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
1. Applicant’s election of Group I, Claims 1-14, with traverse, drawn to a method of producing an aromatic compound or salt thereof, for examination in the reply filed on 6/30/26 is acknowledged.
Applicants argue that “However, the cited art (WO 2021/241508 Al and JP 2002-191370 ) do not disclose that an MFS transporter is involved in the transport of aromatic compounds. Therefore, the cited art does not provide any teaching or suggestion that enhancing the expression of an MFS transporter would increase the productivity of aromatic compounds. Such a conclusion cannot be derived from the cited art.
2. Applicants’ arguments are considered and found to be persuasive. Accordingly, the restriction requirement between Group I (claims 1-15) and Group II (claims 16-22) is withdrawn.
3. All the pending claims 1-22 are under consideration in this Office Action.
4. Because all claims have been rejoined, the restriction requirement as set forth in the Office action mailed on 3/31/26 is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
5. Priority
Receipt is acknowledged of papers (foreign priority filed 12/7/21) submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
6. Drawings
The drawings filed on 9/25/20 are acknowledged.
7. Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant's cooperation is requested in correcting any errors of which applicant may become aware in the specification.
8. The following is a quotation 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.
Written Description
Claims 1-22 are rejected under of 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, as containing 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(s), at the time the application was filed, had possession of the claimed invention.
Claims 1-22 are drawn to the following genus claims.
1. A method for producing an aromatic compound or a salt thereof, comprising culturing a transformed cell with enhanced expression of a multi-pass transmembrane polypeptide represented by (A) or (B): (A) a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 2, or (B) a polypeptide consisting of an amino acid sequence having at least 76% identity to the amino acid sequence represented by SEQ ID NO: 2.
2. The method according to claim 1, wherein the polypeptide consisting of an amino acid sequence having at least 76% identity to the amino acid sequence represented by SEQ ID NO: 2 in (B) is a polypeptide represented by any of (B1) to (B3): (B1) a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 4 or an amino acid sequence having 90% or higher identity to the amino acid sequence represented by SEQ ID NO: 4, (B2) a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 6 or an amino acid sequence having 90% or higher identity to the amino acid sequence represented by SEQ ID NO: 6, or (B3) a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 8 or an amino acid sequence having 90% or higher identity to the amino acid sequence represented by SEQ ID NO: 8.
3. The method according to claim 1, wherein a polynucleotide encoding the multi-pass transmembrane polypeptide represented by (A) or (B) is contained in an expressible state.
4. The method according to claim 1, wherein the culture culturing is performed in the presence of a saccharide.
5. The method according to claim 1, wherein a host of the transformed cell is a microbial cell with improved 3-dehydroshikimic acid-producing activity.
6. The method according to claim 5, wherein the microbial cell with improved 3-dehydroshikimic acid-producing activity is a cell subjected to any one or more of genetic manipulations (i), (ii), (iii), or (iv): (i) enhancement of one or more genes selected from the group consisting of dehydroshikimate dehydratase gene, dehydroquinate dehydratase gene, quinate dehydrogenase gene, and shikimate dehydrogenase gene, (ii) enhancement of one or more genes selected from a gene group involved in the shikimic acid synthesis pathway consisting of 2-dehydro-3-deoxyarabinoheptonate aldolase gene, 3-dehydroquinate synthase gene, and shikimate dehydrogenase gene, (iii) enhancement of one or more genes selected from a gene group involved in the pentose phosphate pathway consisting of glucose-6-phosphate dehydrogenase gene, 6-phosphogluconolactonase gene, phosphogluconate dehydrogenase gene, ribose-5-phosphate isomerase gene, ribulose-5-phosphate-3-epimerase gene, transketolase gene, and transaldolase gene, or (iv) enhancement of a gene encoding a polypeptide having 3,4-dihydroxybenzoate hydroxylase activity.
7. The method according to claim 5, wherein the microbial cell is a coryneform bacterium.
8. The method according to claim 7, wherein the coryneform bacterium is a bacterium of the genus Corynebacterium.
9. The method according to claim 8, wherein the bacterium of the genus Corynebacterium is Corynebacterium glutamicum, Corynebacterium efficiens, Corynebacterium ammoniagenes, Corynebacterium halotolerance, Corynebacterium alkanolyticum, Corynebacterium crenatum, Corynebacterium crudilactis, or Corynebacterium callunae.
10. The method according to claim 8, wherein the bacterium of the genus Corynebacterium is Corynebacterium glutamicum.
11. The method according to claim 1, wherein the aromatic compound or the salt thereof is an aromatic compound derived from 3-dehydroshikimic acid or a salt thereof.
12. The method according to claim 11, wherein the aromatic compound or the salt thereof is gallic acid, protocatechuic acid, catechol, L-DOPA, 2,4-pyridinedicarboxylic acid, 2,5-pyridinedicarboxylic acid, 4-hydroxybenzoic acid, 4-aminobenzoic acid, 4-amino-3-hydroxybenzoic acid, or a salt thereof.
13. The method according to claim 11, wherein the aromatic compound or the salt thereof is gallic acid, protocatechuic acid, L-DOPA, 4-hydroxybenzoic acid, 4-amino-3-hydroxybenzoic acid, or a salt thereof.
14. The method according to claim 11, wherein the aromatic compound or the salt thereof is gallic acid, protocatechuic acid, or a salt thereof.
15. A transformed cell with enhanced expression of a multi-pass transmembrane polypeptide represented by (A) or (B): (A) a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 2, or (B) a polypeptide consisting of an amino acid sequence having at least 76% identity to the amino acid sequence represented by SEQ ID NO: 2, wherein a microbial cell with improved 3-dehydroshikimic acid-producing activity is used as a host.
16. The transformed cell according to claim 15, wherein the microbial cell with improved 3-dehydroshikimic acid-producing activity is a cell subjected to any one or more of genetic manipulations (i), (ii), (iii), and (iv): (i) enhancement of one or more genes selected from the group consisting of dehydroshikimate dehydratase gene, dehydroquinate dehydratase gene, quinate dehydrogenase gene, and shikimate dehydrogenase gene, (ii) enhancement of one or more genes selected from a gene group involved in the shikimic acid synthesis pathway consisting of 2-dehydro-3-deoxyarabinoheptonate aldolase gene, 3-dehydroquinate synthase gene, and shikimate dehydrogenase gene, (iii) enhancement of one or more genes selected from a gene group involved in the pentose phosphate pathway consisting of glucose-6-phosphate dehydrogenase gene, 6-phosphogluconolactonase gene, phosphogluconate dehydrogenase gene, ribose-5-phosphate isomerase gene, ribulose-5-phosphate-3-epimerase gene, transketolase gene, and transaldolase gene, or (iv) enhancement of a gene encoding a polypeptide having 3,4-dihydroxybenzoate hydroxylase activity.
17. The transformed cell according to claim 15, wherein the polypeptide consisting of an amino acid sequence having at least 76% identity to the amino acid sequence represented by SEQ ID NO: 2 in (B) is a polypeptide represented by any of (B1) to (B3): (B1) a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 4 or an amino acid sequence having 90% or higher identity to the amino acid sequence represented by SEQ ID NO: 4, (B2) a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 6 or an amino acid sequence having 90% or higher identity to the amino acid sequence represented by SEQ ID NO: 6, or (B3) a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 8 or an amino acid sequence having 90% or higher identity to the amino acid sequence represented by SEQ ID NO: 8.
18. The transformed cell according to claim 15, wherein a polynucleotide encoding the multi-pass transmembrane polypeptide represented by (A) or (B) is contained in an expressible state.
19. The transformed cell according to claim 15, wherein the microbial cell is a coryneform bacterium.
20. The transformed cell according to claim 19, wherein the coryneform bacterium is a bacterium of the genus Corynebacterium.
21. The transformed cell according to claim 20, wherein the bacterium of the genus Corynebacterium is Corynebacterium glutamicum, Corynebacterium efficiens, Corynebacterium ammoniagenes, Corynebacterium halotolerance, Corynebacterium alkanolyticum, Corynebacterium crenatum, Corynebacterium crudilactis, or Corynebacterium callunae.
22. The transformed cell according to claim 20, wherein the bacterium of the genus Corynebacterium is Corynebacterium glutamicum.
“To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“ [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP 2163.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co., the court stated:
“A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials. Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284-85 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus. . . .”). Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398. In University of California v. Eli Lilly & Co., 43 USPQ2d 1938, the Court of Appeals for the Federal Circuit has held that “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials”. As indicated in MPEP § 2163, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show that Applicant was in possession of the claimed genus. In addition, MPEP § 2163 states that a representative number of species means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gostelli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d at 1012, 10 USPQ2d at 1618.
In the instant case the scope of the instant claims encompass:
A method for producing an aromatic compound or a salt thereof, comprising culturing a transformed cell with enhanced expression of a multi-pass transmembrane polypeptide represented by (A) or (B): (A) a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 2, or (B) a polypeptide consisting of an amino acid sequence having at least 76% identity to the amino acid sequence represented by SEQ ID NO: 2 (claim 1 for example); or A transformed cell with enhanced expression of a multi-pass transmembrane polypeptide represented by (A) or (B): (A) a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 2, or (B) a polypeptide consisting of an amino acid sequence having at least 76% identity to the amino acid sequence represented by SEQ ID NO: 2, wherein a microbial cell with improved 3-dehydroshikimic acid-producing activity is used as a host (claim 15 for example).
The instant specification describes - A method for producing an aromatic compound or a salt thereof, comprising culturing a transformed cell with enhanced expression of a multi-pass transmembrane polypeptide of (A) or (B): (A) a polypeptide consisting of the amino acid sequence of SEQ ID NO: 2, or (B) a polypeptide consisting of an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 2, wherein the aromatic compound or the salt thereof is gallic acid and protocatechuic acid (claim 1, the 2 species described in Table 3, [0176] of the published application US 20250019728 A1);
or A transformed cell with enhanced expression of a multi-pass transmembrane polypeptide of (A) or (B): (A) a polypeptide consisting of the amino acid sequence of SEQ ID NO: 2, or (B) a polypeptide consisting of an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 2, wherein a microbial cell with improved 3-dehydroshikimic acid-producing activity is used as a host and resulting in increased production of gallic acid and protocatechuic acid (claim 15, the 2 species described in Table 3, [0176] of the published application US 20250019728 A1).
Moreover, there is no structure/function correlation which would allow one of skill in the art to determine which structural modifications can be made and claims as written require an extremely large structurally and functionally variable genus, wherein the amino acid sequence having at least 76% identity to the amino acid sequence of SEQ ID NO: 2, i.e. altering the sequence by 24% or by 95 amino acids in the 398 amino acid long SEQ ID NO: 2.
An argument can be made that the recited genus gene or protein can be selected via structural correlation isolate those recited gene or polypeptides related to SEQ ID NO: 2 (among others) recited in the claims. However, as described below, the art clearly teaches the "Practical Limits of Function Prediction":
A. Devos et al., (Proteins: Structure, Function and Genetics, 2000, Vol. 41: 98-107), teach that the results obtained by analyzing a significant number of true sequence similarities, derived directly from structural alignments, point to the complexity of function prediction. Different aspects of protein function, including (i) enzymatic function classification, (ii) functional annotations in the form of key words, (iii) classes of cellular function, and conservation of binding sites can only be reliably transferred between similar sequences to a modest degree. The reason for this difficulty is a combination of the unavoidable database inaccuracies and plasticity of proteins (Abstract, page 98) and the analysis poses interesting questions about the reliability of current function prediction exercises and the intrinsic limitation of protein function prediction (Column 1, paragraph 3, page 99) and conclude that "Despite widespread use of database searching techniques followed by function inference as standard procedures in Bioinformatics, the results presented here illustrate that transfer of function between similar sequences involves more difficulties than commonly believed. Our data show that even true pair-wise sequence relations, identified by their structural similarity, correspond in many cases to different functions (column 2, paragraph 2, and page 105).B. Whisstock et al., (Quarterly Reviews of Biophysics 2003, Vol. 36 (3): 307-340,) also highlight the difficulties associated with "Prediction of protein function from protein sequence and structure": "To reason from sequence and structure to function is to step onto much shakier ground", closely related proteins can change function, either through divergence to a related function or by recruitment for a very different function, in such cases, assignment of function on the basis of homology, in the absence of direct experimental evidence, will give the wrong answer (page 309, paragraph 4), it is difficult to state criteria for successful prediction of function, since function is in principle a fuzzy concept. Given three sequences, it is possible to decide which of the three possible pairs is most closely related. Given three structures, methods are also available to measure and compare similarity of the pairs. However, in many cases, given three protein functions, it would be more difficult to choose the pair with most similar function, although it is possible to define metrics for quantitative comparisons of different protein sequences and structures, this is more difficult for proteins of different functions (page 312, paragraph 5), in families of closely related proteins, mutations usually conserve function but modulate specificity i.e., mutations tend to leave the backbone conformation of the pocket unchanged but to affect the shape and charge of its lining, altering specificity (page 313, paragraph 4), although the hope is that highly similar proteins will share similar functions, substitutions of a single, critically placed amino acid in an active-site residue may be sufficient to alter a protein's role fundamentally (page 323, paragraph 1).C. This finding is reinforced in the following scientific teachings for specific proteins in the art that suggest, even highly structurally homologous polypeptides do not necessarily share the same function and many functionally similar proteins will have little or no structural homology to disclosed proteins. For example, proteins having similar structure have different activities (structure does not always correlate to function); Witkowski et al., (Biochemistry 38:11643-11650, 1999) teaches that one conservative amino acid substitution transforms a beta -ketoacyl synthase into a malonyl decarboxylase and completely eliminates beta-ketoacyl synthase activity. The art also teaches that functionally similar molecules have different structures; Kisselev L., (Structure, 2002, Vol. 10: 8-9) teach that polypeptide release factors in prokaryotes and eukaryotes have same function but different structures.
As stated above, no information beyond the characterization of specific structure by polypeptide having the sequence of SEQ ID NO: 2 (or a sequence 95% identical to SEQ ID NO: 2) having recited activity has been provided by the applicants’, which would indicate that they had the possession of the claimed production genus of polypeptides and the encoding polynucleotides having recited activity. The claimed genera of polypeptides and the encoding polynucleotides have widely variable structures and associated functions. As it is discussed above, a minor changes in structure may result in changes affecting function, since, the specification provided no additional information (species/variant/mutant) correlating structure with function, and one skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed. Furthermore, "Possession may not be shown by merely describing how to obtain possession of members of the claimed, genus or how to identify their common structural features" (See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895). A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the .gene does (function), rather what it is (structure), see University of California v. Eli Lilly & Co., 43 USPQ2d 1938, thus above claims lack adequate written description. Therefore one of skill in the art would not recognize from the disclosure that applicants were in possession of the claimed invention.
Applicants' are referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
9. Claim Rejections - 35 USC § 112 (second paragraph)
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 1-22 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 pre-AIA the applicant regards as the invention.
Claims 1-3, 15 & 17 recite the phrase – “polypeptide or amino acid sequence represented by”. The claims are unclear specifically about the use of phrase “represented by” and may include other representative sequences. Deletion of the phrase “represented by” is suggested to overcome this rejection.
Claims 4-14, 16 & 18-22 are included in the rejection for failing to correct the defect present in the base claim(s).
10. No claim is allowed.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to TEKCHAND SAIDHA whose telephone number is (571)272-0940. The examiner can normally be reached on M-F 8.00-5.30. 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, Robert B Mondesi can be reached on 408 918 7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TEKCHAND SAIDHA/
Primary Examiner, Art Unit 1652
Recombinant Enzymes, Hoteling
Telephone: (571) 272-0940
Fax: (571) 273-0940
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