DETAILED ACTION
Status of Application
Claims 1-11 are pending
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A preliminary amendment of claims 1-10 as submitted in a communication filed on 07/05/2024 is acknowledged.
Applicant’s election with traverse of Group I, claims 1-10, drawn to a method for synthesis of L-phosphinothricin, as submitted in communication filed on 06/24/2026 is acknowledged. Applicant’s traverse is on the grounds that it would not pose an undue burden on the Examiner to examine all the claims together. Upon further consideration, the previous restriction requirement between Groups I and II are hereby withdrawn. Groups I and II will be rejoined for examination on the merits.
Claims 1-11 are at issue and will be examined to the extent they encompass the elected invention.
Priority
Acknowledgment is made of a claim for foreign priority under 35 U.S.C. 119(a)-(d) to 202310827168.9 filed on 07/07/2023. Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
Drawings
The drawings submitted on 07/05/2024 have been reviewed and are accepted by
the examiner for examination purposes.
Specification Objections
The specification is objected to due to missing primer sequence identifiers (Pages 10-11). Appropriate correction is required. See requirements below.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claims Objections
Claims 2-5 are objected to due to the recitation of steps “(1)” and/or “(2)”. Since claim numbering already uses Arabic numerals, to avoid confusion, the itemization labels should be replaced with, for example, (i), (ii) and (iii), or (a), (b) and (c). Appropriate correction is required.
Claim 6 is objected to due to the recitation of “substrate added to the reation system is 200-800 mM; the final concentraiont of isopropanol added to the reaction system”. It should be amended to recite “substrate added to the reaction system is 200-800 mM; the final concentration of isopropanol added to the reaction system”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA )
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, 6, and 9 (claims 2-5, and 7-8, and 10-11 dependent thereon) are indefinite due to the recitation of “wet cells” for the following reasons: It is unclear because it lacks objective boundaries and the term is not well-defined in the art, making it unclear which cells meets the limitation. For examination purposes, the term “wet cells” will be interpreted as cells. Correction is required.
Claims 1, 7, and 9-11 (claims 2-6, and 8 dependent thereon) are indefinite in the recitation of “amino acid sequence shown as SEQ ID NO”, for the following reason: “shown as” is used as a reference for a sequence example. Therefore, the limitations of the sequences are unclear in this case, SEQ ID Nos will be interpreted as examples that can have variation. For examination purposes, the claims do not require a variant of a sequence that comprise all of the sequence. Correction is required.
Claim Rejections - 35 USC § 112(a) or First Paragraph (pre-AIA )
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 1-11 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
As stated in MPEP 2111.01, during examination, the claims must be interpreted as broadly as their terms reasonably allow.
Claims 1-11 are directed in part to a method of producing L-phosphinothricin from PPO by using any phosphinothricin dehydrogenase, or any phosphinothricin dehydrogenase mutants of SEQ ID NO:2 not having a Val and/or Met residue at the positions corresponding to 73 and 91, respectively, of SEQ ID NO:2. See claim rejections under 35 usc 112(b) for claim interpretation.
While the specification is limited to the disclosure of a single polypeptide, having the function of using PPO as a substrate to produce L-phosphinothricin, a Lysinibacillus composti glutamate dehydrogenase of SEQ ID NO:2 or a mutant thereof consisting of V73C and/or M91G, it provides no clue as to the structural elements required in any phosphinothricin dehydrogenase, or any phosphinothricin dehydrogenase mutant of SEQ ID NO:2 that use PPO as a substrate to produce L-phosphinothricin.
A sufficient written description the phosphinothricin dehydrogenases and the phosphinothricin dehydrogenase mutants of SEQ ID NO:2 may be achieved by a recitation of structural features common to members of the required phosphinothricin dehydrogenases and phosphinothricin dehydrogenase mutants of SEQ ID NO:2. However, in the instant case, there is no recited structural feature which is representative of all the members of the required phosphinothricin dehydrogenases and phosphinothricin dehydrogenase mutants of SEQ ID NO:2 recited in the claims, and there is no information as to which are the structural elements of the dehydrogenases that are essential for the recited function of using PPO as a substrate to produce L-phosphinothricin, or a correlation between structure and function which would provide those unknown structural features. Furthermore, while one could argue that the species disclosed is representative of the structure of all the phosphinothricin dehydrogenases and phosphinothricin dehydrogenase mutants of SEQ ID NO:2 required, it is noted that the art teaches examples of different glutamate dehydrogenases having different enzymatic activities for L-phosphinothricin synthesis. For example, Wang et al. (ACS Catalysis 12.21 (2022): 13619-13629) teach that wildtype glutamate dehydrogenase (CdGluDH) has no enzymatic activity on L-phosphinothricin while mutants exhibited enzymatic activity (Figure 7). Therefore, since the structural differences of glutamate dehydrogenases may result in changes affecting conversion of PPO to L-phosphinothricin, and no additional information correlating structure with the desired functional characteristics has been provided, one cannot reasonably conclude that the species disclosed are representative of the structure of all the phosphinothricin dehydrogenases, and phosphinothricin dehydrogenase mutants of SEQ ID NO:2 not having a Val and/or Met residue at the positions corresponding to 73 and 91, respectively, of SEQ ID NO:2, that can use PPO as a substrate to produce L-phosphinothricin as required by the claimed process. Therefore, one of ordinary skill in the art would not recognize from the disclosure that Applicant was in possession of the claimed invention.
Claims 1-11 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 method of producing L-phosphinothricin with a single polypeptide, having the function of using PPO as a substrate to produce L-phosphinothricin, a Lysinibacillus composti glutamate dehydrogenase of SEQ ID NO:2 or a mutant thereof consisting of V73C and/or M91G, does not reasonably provide enablement for a method of producing L-phosphinothricin from PPO by using any phosphinothricin dehydrogenase, or any phosphinothricin dehydrogenase mutant of SEQ ID NO:2 not having a Val and/or Met residue at the positions corresponding to 73 and 91, respectively, of SEQ ID NO:2. 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/or use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2nd 1400 (Fed. Cir. 1988)) as follows: 1) quantity of experimentation necessary, 2) the amount of direction or guidance presented, 3) the presence and absence of working examples, 4) the nature of the invention, 5) the state of prior art, 6) the relative skill of those in the art, 7) the predictability or unpredictability of the art, and 8) the breadth of the claims. The factors which have led the Examiner to conclude that the specification fails to teach how to make and/or use the claimed invention without undue experimentation, are addressed in detail below.
The breadth of the claims. Claims 1-11 broadly encompass a method of producing L-phosphinothricin from PPO by using any phosphinothricin dehydrogenase, or any phosphinothricin dehydrogenase mutant of SEQ ID NO:2 not having a Val and/or Met residue at the positions corresponding to 73 and 91, respectively, of SEQ ID NO:2. The enablement provided is not commensurate in scope with the claims due to the lack of knowledge regarding the structure/identity of any phosphinothricin dehydrogenase, or any phosphinothricin dehydrogenase mutant of SEQ ID NO:2 not having a Val and/or Met residue at the positions corresponding to 73 and 91, respectively, of SEQ ID NO:2 that can use PPO as a substrate to produce L-phosphinothricin. In the instant case, the specification enables a single polypeptide, having the function using PPO as a substrate to produce L-phosphinothricin, a Lysinibacillus composti glutamate dehydrogenase of SEQ ID NO:2 or a mutant thereof consisting of V73C and/or M91G.
The amount of direction or guidance presented and the existence of working examples. The specification discloses a single polypeptide, having the function of using PPO as a substrate to produce L-phosphinothricin, a Lysinibacillus composti glutamate dehydrogenase of SEQ ID NO:2 or a mutant thereof consisting of V73C and/or M91G. However, the specification fails to provide any clue as to the structural elements required in any phosphinothricin dehydrogenase, or any phosphinothricin dehydrogenase mutant of SEQ ID NO:2 not having a Val and/or Met residue at the positions corresponding to 73 and 91, respectively, of SEQ ID NO:2, that can use PPO as a substrate to produce L-phosphinothricin. No correlation between structure and function has been presented.
The state of prior art, the relative skill of those in the art, and the predictability or unpredictability of the art. The structure of an enzyme determines its structural and functional properties. While the art discloses a limited number of phosphinothricin dehydrogenases, neither the specification nor the art provide a correlation between structure and function such that one of skill in the art can envision the structure of any phosphinothricin dehydrogenase, or any phosphinothricin dehydrogenase mutant of SEQ ID NO:2 not having a Val and/or Met residue at the positions corresponding to 73 and 91, respectively, of SEQ ID NO:2, that can use PPO as a substrate to produce L-phosphinothricin. The art clearly teaches of different glutamate dehydrogenases having different enzymatic activities for L-phosphinothricin synthesis. For example, Wang et al. (ACS Catalysis 12.21 (2022): 13619-13629) teach that CdGluDH has no enzymatic activity regarding L-phosphinothricin synthesis while the mutants exhibited enzymatic activity (Figure 7).
The quantity of experimentation required to practice the claimed invention based on the teachings of the specification. While methods of determining enzyme activity were known in the art at the time of the invention, it was not routine in the art to screen by a trial and error process for an essentially infinite number of phosphinothricin dehydrogenases and phosphinothricin dehydrogenase mutants of SEQ ID NO:2 to find a dehydrogenase with the desired function to use PPO as a substrate to produce L-phosphinothricin. In the absence of (i) a rational and predictable scheme for selecting those dehydrogenases most likely to have the desired functional features, (ii) a correlation between structure and the ability to use PPO as a substrate to produce L-phosphinothricin, one of skill in the art would have to test an infinite number of dehydrogenases.
Therefore, taking into consideration the extremely broad scope of the claims, the lack of guidance, the amount of information provided, the lack of knowledge about a correlation between structure and the desired function, the high degree of unpredictability in the prior art, one of ordinary skill in the art would have to go through the burden of undue experimentation in order to practice the claimed invention. Thus, Applicant has not provided sufficient guidance to enable one of ordinary skill in the art to make and use the invention in a manner reasonably correlated with the scope of the claims.
Conclusion
No claim is in condition for allowance.
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/S.L.S./Examiner, Art Unit 1652
/ROBERT B MONDESI/Supervisory Patent Examiner, Art Unit 1652
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