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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Specification
The amendment to the specification filed on 5/11/26 has been entered.
The abstract of the disclosure is objected to because there is another part of the specification (drawing) in the abstract. This instant application is not directed to a chemical composition but a biological composition. 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).
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The use of the term ATCC, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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.
Claims 1, 2 and 5-20 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.
The claimed invention embraces a very large of genus of mutant pyruvate carboxylase (pyc) gene promoter in Corynebacterium glutamicum having an enhanced promoter activity as compared to a pyruvate carboxylase gene promoter having the sequence set forth in SEQ ID NO: 21. The functional limitation ‘having an enhanced promoter activity as compared to a pyruvate carboxylase gene promoter having the sequence set forth in SEQ ID NO: 21 ‘is considered the desired biological activity of the mutant pyc gene promoter.
The broadest reasonable interpretation of the claimed product embraces a nucleotide sequence comprising a mutated pyruvate carboxylase (pyc) gene promoter that has enhanced promoter activity compared to a known pyc gene promoter set forth in SEQ ID NO: 21, wherein the sequence (i) has one or more mutated nucleotides corresponding to SEQ ID NO: 21, (ii) a nucleotide sequence with at least 50% complementary to the sequence set forth in (i), (iii) a nucleotide sequence that is reverse complementary to sequence capable of hybridizing with the nucleotide sequence of (i) or (ii) under high-stringent hybridization conditions or very high-stringent hybridization conditions as set forth in page 14 of the specification, and (iv) at least 90% sequence identity to the nucleotide sequence set forth in (i) or (ii); and the sequence does not comprise SEQ ID NO: 60.
SEQ ID NO: 60 appears to the sequence for positions 279 to 371 of SEQ ID NO: 21 and was known in the prior art for the pyc gene promoter. The art of record discloses that the pyc gene promoter was well known in the prior art.
Page 13 provides a definition for the terms high-stringent and very high stringent conditions.
The specification discloses working examples for screening and strength characterization of pyc gene promoter mutants of Corynebacterium glutamicum. See example 2. The core region of the gene promoter was mutated, but several nucleotides were not changed. See SEQ ID NO: 61. The present disclosure performed an initial screening on more than 10,000 clones and as shown in Figure 2 about 30 mutants with enhanced fluorescence intensity were obtained. The present disclosure successfully obtained 20 different promoter mutants (SEQ ID NOs: 1-20) with improved intensity as compared to the wild-type promoter and the ranged of the increase folds was from 1.8 folds to 16.1 folds. All of the sequences had SEQ ID NO: 61. The specification does not appear to provide the sequence for all of the 30 mutants.
The prior art (SEQ ID NO: 14 in US 20090246836 and SEQ ID NO: 44 in US 8912313) discloses constructs comprising a nucleotide sequence that would be embraced by the instant claims, but the prior art does teach if these constructs possess the desired biological activity.
CN10951662A (published 4/3/20, cited on an IDS) discloses a construct for producing lysine at a high yield using a Corynebacterium bacteria comprising a mutated pyc promoter. See the English translation of ‘662, pages 1-29. It appears that a pyc promoter for a gene encoding L-lysine is modified by changing a region of the promoter. The ATCC13032 genome was used as the template. The description in the English translation of ‘662 for the working examples for the bacterium is difficult to determine the structural limitation of the construct. A sequence search of the prior art does not appear to disclose that sequences disclosed in ‘662 read on the claimed SEQ ID NOs: in instant claims 3 and 4. Several of the sequences, including SEQ ID NOs: 17-19 of ‘’622 appear to have the core sequence set forth in claim 2. The sequences appear to be used in a bacterium to increase lysine production.
Neither the specification or the art of record disclose any sequence not having SEQ ID NO: 61 would have the desired biological activity. Thus, the specification provides written support for instant claims 2-4 because the working examples show that the essential structure for the desired biological activity of the promoter.
However, the nucleotide sequences embraced by the instant claims are broader than SEQ ID NO: 61 recited in claim 2 and the specification does not describe what in position, including positions 279 to 317 of the nucleotide sequence of SEQ ID NO: 21 not comprising SEQ ID NO: 61 can be mutated and observe the desired biological activity.
While one of skill in the art could make the sequences, the skilled artisan as shown in example 2 of the as-filed specification would have to further experiment to determine if any sequence has the desired activity in view of the written description in the instant disclosure for what sequences not including SEQ ID NO: 61 are required to observe the activity.
The written description requirement for the claimed genus is not satisfied through sufficient description of a representative number of species. SEQ ID NO: 61 and SEQ ID NOs: 1-20 are not considered a representative number of species that would adequately described and represent the entire genus of mutant promoters. Items (i)-(iv) of instant claim 1 embrace a large number of sequences that do not require SEQ ID NO: 61 and not comprise SEQ ID NO: 60. SEQ ID NO: 21 is 373 nucleotides in length. A mutant that has one or mutated nucleotides in a core region corresponding to position 279 to position 317 of a promoter set forth in SEQ ID NO: 21 embraces a mutant having one or all of the nucleotides substituted in the core region. A sequence that has 90% sequence identity has 336 nucleotides of SEQ ID NO: 21. The sequences embraced by item (ii) or (iii) are even broader than 90% sequence identity and embrace a very large number of nucleotide sequences. A skilled artisan would possess the knowledge that substituting one or more nucleotides in the mutant could modulate (abolish, increase, decrease) the activity of the promoter. There is a substantial variation within the genus of sequences and the specification does not describe a sufficient variety of species to reflect the variation within the genus. It appears that SEQ ID NO: 61 is required for the desired biological activity. See Enzo Biochem., 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)(“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). See also MPEP §2163.
In view of the foregoing, it is clear that the specification of the instant disclosure fails to convey to the skilled artisan that the applicant had possession of the claimed genus of mutant pyruvate carboxylase gene promoter in Corynebacterium glutamicum having an enhanced promoter activity as compared to a pyruvate carboxylase gene promoter having the sequence set forth in SEQ ID NO: 21 in the instant claims 1, 2, and 5-20 as of the effective filing date.
Claims 9, 10, 16, and 17 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 for enhancing a transcriptional level of a gene comprising operably linking the pyruvate carboxylase gene promoter of claim 1 to a gene or a method of preparing a reagent or kit for enhancing a transcriptional level of a gene comprising providing the pyruvate carboxylase gene promoter of claim and a gene, does not reasonably provide enablement for utilizing the mutant of the pyruvate carboxylase gene promoter according to claim 1. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The pre-amble of each claimed method broadly embraces different methods requiring different method steps and materials. The method step of utilizing the mutant of the pyruvate carboxylase gene promoter according to claim 1 is very broad and does not provide a nexus between the pre-amble and the method steps of claimed methods to compete the claimed methods. The step of utilizing does not provide any active steps for one of skill in the art to carry out the claimed method to complete the pre-amble of the claims.
Thus, the claims are not fully enabled.
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.
Claim 15 is 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 15 contains the trademark/trade name ATCC. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a cell line and, accordingly, the identification/description is indefinite
.
Improper Markush Rejection
Claims 9, 10, 16, and 17 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of method of enhancing a transcriptional level of a gene or preparing a reagent or kit for enhancing a transcriptional level of a gene is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons. Each method is directed to a different method requiring different method steps and materials. One is a method of using the promoter of claim 1 and the other is making a reagent or kit comprising the promoter of claim 1.
The Markush grouping of method of producing a target product or preparing a reagent or kit for use in the production of a target product is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons. Each method is directed to a different method requiring different method steps and/or materials.
The Markush grouping of method of preparing a protein or preparing a reagent or kit for use in the preparation of a protein is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons. Each method requires different method steps and materials.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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.
Claims 1, 2, 4-17 and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over CN110951662 (published on 4/3/20, cited on an IDS, see pages 1-29 of attached English translation) taken with Walter (US 20160265072).
The broadest reasonable interpretation (BRI) of the claimed product embraces a nucleotide sequence comprising a mutated pyruvate carboxylase (pyc) gene promoter that has enhanced promoter activity compared to a known pyc gene promoter set forth in SEQ ID NO: 21, wherein the sequence (i) has one or more mutated nucleotides corresponding to SEQ ID NO: 21; (ii) a nucleotide sequence that is a reverse complement to the sequence set forth in (i); (iii) a nucleotide sequence that is reverse complementary to sequence capable of hybridizing with the nucleotide sequence of (i) or (ii) under high-stringent hybridization conditions or very high-stringent hybridization conditions as set forth in page 14 of the specification; and (iv) at least 90% sequence identity to the nucleotide sequence set forth in (i) or (ii); and the sequence does not comprise SEQ ID NO: 60.
There is no minimum or maximum length limit for the sequence.
The English translation of the disclosure of ‘662 teaches a pyruvate carboxylase promoter which enhances promoter activity by changing the promoter -10 region and the extended sequence thereof, as shown in SEQ ID NO 19 or 20. The reference also discloses high-yield lysine-producing Corynebacterium glutamicum (C. glutamicum) and methods and applications thereof. The ATCC 13032 C. glutamicum genome was used to produce the modified promoter. Thus, the pyc promoter taught by ‘662 reads on the claimed product because it is a pyc promoter meeting the structural limitation of item (i) of instant claim 1.
‘662 does not specifically teach the functional limitation (has an enhanced promoter activity as compared to a pyruvate carboxylase gene promoter having the sequence set forth in SEQ ID NO: 21) for the bacteria used for expressing lysine.
However, Walter teaches a pyruvate carboxylase gene promoter having the sequence set forth in SEQ ID NO: 21 was well-known in the prior art. See SEQ ID NO: 1.
L-lysine, are produced by fermentation by strains of coryneform bacteria, especially Corynebacterium glutamicum, or by strains of the Enterobacteriaceae family, especially Escherichia coli. Owing to the considerable economic importance, there are constant efforts to improve the production processes. Process improvements can relate to technical measures in fermentation, for example stirring and supplying oxygen, or to the composition of the nutrient media, for example the sugar concentration during fermentation, or to work-up to the product form for example by ion exchange chromatography or to the intrinsic performance properties of the microorganism itself. See paragraph 4.
Walter teaches method steps for producing organic chemical compounds by fermentation using a microorganism, wherein the compound is an L-amino acid selected from the group L-threonine, L-isoleucine, L-lysine, L-methionine, L-ornithine, L-proline, L-valine, L-leucine and L-tryptophan. See claims 1-16
It would have been prima facie obvious to a person of ordinary skill in the art before the time of the effective filing date to use Corynebacterium comprising the mutated promoter and produce lysine and compare it to a Corynebacterium comprising SEQ ID NO: 21 taught by Walter, namely to arrive at the claimed invention. In view of the BRI of claim 1 (items (i) or (iv)), the mutant promoter taught by ‘622 is embraced by the instant mutant promoter. Several of the sequences, including SEQ ID NOs: 17-19 of ‘’622 appear to have the core sequence set forth in instant claim 2. The sequences appear to be used in a bacterium to increase lysine production. One of ordinary skill in the art would have been motivated to study the Corynebacterium taught by ‘622 compared to the Corynebacterium known in the prior art to determine if it has an enhanced promoter activity. In view of ‘622, there would be a reasonable expectation of success that the promoter taught by ‘622 would possess the desired biological activity because ‘622 teaches that is produced a higher lysine yield. The limitation “utilizing the mutant of the pyruvate carboxylase gene promoter according to claim 1” in claims 9, 10, and 16-17 does not embrace any active method steps and all that is required is using a C. glutamicum comprising the mutated promoter to produce lysine, which was taught by ‘662. It would have been obvious to try make C. glutamicum ATCC 13032 comprising the mutated promoter to study producing an organic compound since ‘622 teaches ATCC-13032 is a well-known host cell for producing a protein of interest. Since the mutated promoter taught by ‘622 would increase the yield of lysine, it would have been obvious for one of ordinary skill in the art try using the Corynebacterium comprising the mutated promoter to produce any of the amino acid(s) set forth in instant claims 17, 19 and 20 and isolate the amino acid(s).
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over ‘622 taken with Walters as applied to claims 1, 2, and 4-17 and 19-20 above, and further in view of Genomatics, Inc. (US 20140127765).
‘622 and Walters do not specifically teach using the method to produce the enzymes set forth in instant claim 18.
However, genes encoding the enzymes set forth in instant claim 18 are well well-known in the prior art as taught by ‘765. For example, see pages 7-31, 50-65, and 82-84 and Figures 1-8. See also MPEP 2141(II)C. Rationales to support rejections under 35 U.S.C. 103 recites, “Prior art is not limited to the references being applied, but includes the understanding of one of ordinary skill in the art.”
It would have been prima facie obvious to a person of ordinary skill in the art before the time of the effective filing date to combine the teaching of ‘622 and Walters taken with ‘765 to ligate the mutant pyc promoter taught by ‘622 to increase yield of any desired protein or enzyme known in the prior art, namely to arrive at the claimed invention. See MPEP 2143(I)E. One of ordinary skill in the art would have been motivated to combine the teaching to try and use the method to enhance expression of any enzyme known in the art prior art as taught by ‘765, including the enzymes set forth in instant claim 18 with a reason\able expectation of success.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
NOTE: the ‘622 reference was used as a 102(a)(1) prior art reference in the 103 rejections set forth above because the applicant did not perfect priority to the foreign application.
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
A sequence search of the prior art does not appear to disclose that sequences disclosed in ‘662 read on the claimed SEQ ID NOs: in instant claims 3 and 4.
Allowable Subject Matter
Claims 3-4 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. The prior art does not teach or suggest the SEQ ID NOs: set forth in these claims.
CN112695036 (published 4/23/21, cited on an IDS) was cited as an X,P reference on an English translation of the international search report filed on 1/18/23. However, the reference has a subset of the inventors and the reference does not qualify as prior art in view of the 102(b)(1)(A) and 102(b)(2)(A) exceptions.
Conclusion
See attached PTO-326 for disposition of claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brian Whiteman whose telephone number is (571)272-0764. The examiner can normally be reached on Monday thru Friday; 6:00 AM to 3:00PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at (571)-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRIAN WHITEMAN/ Primary Examiner, Art Unit 1636
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