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 .
2. The Office Action mailed on December 22, 2025, has been vacated because an amendment to the claims was not entered.
3. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on December 20, 2024, has been entered.
Claim Disposition
4. Claims 2-3, 6 and 10-17 are cancelled. Claims 1, 4-5, 7-9 and 18-20 are pending and are under examination.
Claim Objection
5. Claims 1, 4-5, 7-9 and 18-20 are objected to because of the following informalities:
For clarity and precision of claim language it is suggested that claim 1 is amended to read,
“wherein the yeast cell converts the 2-(hydroxysulfanyl)-hercynine to ergothioneine, [[and]] wherein the yeast cell is selected from the group consisting of….., wherein the first heterologous enzyme and second heterologous enzyme are:
Neurospora crassa……………………..
CpEgt1 (SEQ ID NO: 6)…..or
Functional variants thereof having at least 90% sequence identity thereto, [[and]] wherein the yeast cell produces ergothioneine with a total titer of…….and wherein the total titer is the sum of…..”. The dependent claims hereto are also included. See also claim 7 with similar language.
For clarity it is suggested that claim 4 is amended to read, “…………i) NcEgt1 and CpEgt2;………..xii) CpEgt1……..or xiii) functional variants thereof…….”.
For clarity and precision of claim language it is suggested that claim 7 is amended to add the transitional phrase ‘and’ between the last two ‘wherein clause’ (i.e. “….wherein…..and wherein…”). The dependent claims hereto are also included.
For clarity it is suggested that claim 7 is amended to read, “A method of producing ergothioneine in a yeast cell, comprising [[the steps of]]:…….wherein the yeast cell [[is]] converts the 2-(hydroxysulfanyl)-hercynine ……”. The dependent claims hereto are also included.
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.
6. Claims 1, 4-5, 7-9 and 18-20 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 as amended is a yeast cell which produces ergothioneine said yeast cell expressing at least one first heterologous enzyme which converts L-histidine and/or L-cysteine to S-hercyn-2-yl-L-cysteine S-oxide and at least one second heterologous enzyme which converts S-hercyn-2-yl-L-cysteine S-oxide to 2-(hydroxysulfanyl)-hercynine wherein the yeast cell converts 2-(hydroxysulfanyl)-hercynine to ergothioneine, [[and]]…. wherein the yeast is selected from the group consisting of : S.cerevisiae, P. pastoris …….. (see claim 1). The invention as claimed in claim 1 is devoid of a structure-function correlation for the variants thereof. The assertion of “functional” does not garner activity and with the fragments there is no guarantee the activity is the same or maintained.
The invention also encompasses a large genus of nucleic acid that could encode the first and second heterologous enzyme. The art generally establishes that several different genes can encode the same protein, thus the invention needs to be adequately described.
The claimed invention encompasses method claims (see, for example, claim 7) for producing ergothioneine with the yeast and also describes a first and second nucleic acid that encodes the first and second heterologous enzymes (see claim 8), with no structural limitations.
It is noted that claim 5 recites a structure for the further expression/over expression of an ergothioneine transporter, such as MsErgT or variants thereof having 90% sequence identity, however, claim 1 needs to stand on its own and it does not rectify all the missing information in independent claim 1.
The claimed invention is not adequately described because it encompasses a large variable genus of structures and products. In addition, there is no nexus between the modified structures and production of the product.
The claimed invention is not commensurate in scope with the disclosure in the specification and over reaches. The claimed invention requires a product that is not adequately described because there is no structure-function correlation provided for the broad variable genus encompassed in the claims. An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. See Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir.1997). Thus, applicant has not demonstrated possession of the invention as claimed. Furthermore, the 'written description' requirement.., serves both to satisfy the inventor's obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed ....The descriptive text needed to meet these requirements varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence." Capon v. Eshhar, 418 F.3d 1349, 1357 (Fed. Cir. 2005). The purpose of the written description requirement "is to ensure that the scope of the right to exclude ... does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification." Reiffin v. Microsoft Corp., 214 F.3d 1342, 1345-46 (Fed. Cir. 2000). The goal of the written description requirement is "to clearly convey the information that an applicant has invented the subject matter which is claimed." In re Barker, 559 F.2d 588, 592 n.4 (CCPA 1977) "A disclosure in an application, to be complete, must contain such description and details as to enable any person skilled in the art or science to which the invention pertains to make and use the invention as of its filing date." In re Glass, 492 F.2d 1228, 1232 (CCPA 1974).
Additionally, Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir.1991), states that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed" (See page 1117). The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed" (See Vas-Cath at page 1116). The skilled artisan cannot envision the detailed chemical structure of the encompassed genus of structures, and therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993).
Accordingly, the claimed invention is determined as lacking adequate written description because applicant has not demonstrated possession of the entire genus encompassed in the claims which is vast with respect to the fusion protein that encompasses mutants and fragments with no asserted activity.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
7. Claim(s) 1 and 7 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by NAGASE & CO. LTD. (WO 2017/150304, of record in the application).
The claimed invention is directed to a yeast cell which produces ergothioneine. WO2017/150304 discloses a method of producing ergothioneine either with one or both of the genes corresponding to Egt1 or Egt2 of Schizosaccharomyces pombe or Egt1 or Egt2 of Neurospora crassa in Actinomycetes, intestinal bacteria or yeast (see pages 3-6 and page 11) and discloses yeast like Saccharomyces and Schizosaccharomyces (see page 10). Therefore the limitations of the claims are met by the reference since any functional variant thereof is included.
Claim Rejections - 35 USC § 103
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.
8. 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.
9. Claim(s) 1, 7-9 and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over NAGASE & CO. LTD. (WO 2017/150304, of record in the application) in view of Database UniProt [Online] 1 May 2013, of record in the application) and Shun et al.(2019, of record in the application).
The claimed invention is directed to a yeast cell which produces ergothioneine. WO2017/150304 discloses a method of producing ergothioneine either with one or both of the genes corresponding to Egt1 or Egt2 of Schizosaccharomyces pombe or Egt1 or Egt2 of Neurospora crassa in Actinomycetes, intestinal bacteria or yeast (see pages 3-6 and page 11) and discloses yeast like Saccharomyces and Schizosaccharomyces (see page 10). The primary reference does not teach CpEgt2 (Claviceps purpurea Egt2), however, the secondary reference discloses the amino acid sequence of the Claviceps purpurea Egt1 and Egt2 polypeptide sequences (see Database Accession No.M1W4M1). The tertiary reference teaches a heterologous overexpression of the Neurospora crassa Egt-1 and -2 genes in the filamentous fungus Aspergillus oryzae. Transformants produced up to 231.0 mg ERG/kg of media corresponding to a 20 times higher production than the wildtype. The ergothioneine transporter Oct1 from the SLC22 transporter family is mentioned (see pages 181-184).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed invention as a whole because the combined teaching of the references render it as obvious. The ordinary skilled worker would be motivated to combine the teaching of the references because they are deemed as analogous art. Moreover, the Supreme Court pointed out in KSR, “a patent composed of several elements is not proved obvious merely by demonstrating that each of its elements was, independently, known in the prior art.” KSR, 127 S. Ct. at 1741. The Court thus reasoned that the analysis under 35 U.S.C. 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the “inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 1741. The Court further advised that “[a] person of ordinary skill is…a person of ordinary creativity, not an automation.” Id. at 1742. Therefore, the claimed invention was obvious to make and use at the time the invention was made and was prima facie obvious.
Moreover, the Supreme Court pointed out in KSR, “a patent composed of several elements is not proved obvious merely by demonstrating that each of its elements was, independently, known in the prior art.” KSR, 127 S. Ct. at 1741. The Court thus reasoned that the analysis under 35 U.S.C. 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the “inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 1741. The Court further advised that “[a] person of ordinary skill is…a person of ordinary creativity, not an automation.” Id. at 1742. Therefore, the claimed invention was obvious to make and use at the time the invention was made and was prima facie obvious.
Response to Arguments
10. Applicant’s comments have been considered in full. Withdrawn objections/rejections will not be addressed herein as applicant’s comments are moot. Note that the rejections of record remain and have been altered to reflect changes made to the claims. Applicant filed an IDS, however, it has been lined through due to an improper date.
Applicant traverses the 112 first paragraph rejection stating that adequate written description is assumed unless or until sufficient evidence or reasoning to the contrary has been presented by the examiner to rebut the presumption; and the applicant indicates that the claims have been amended. This argument is not persuasive because the rejection was made to alert applicant that the description provided is not commensurate in scope with the claims. The claimed invention is primarily described by activity and not structure. There is language of for example, functional variants thereof with at least 90% sequence identity does not mean the activity is retained and this doesn’t give a specific structure. Applicant is reminded that the 'written description' requirement.., serves both to satisfy the inventor's obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed ....The descriptive text needed to meet these requirements varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence." Capon v. Eshhar, 418 F.3d 1349, 1357 (Fed. Cir. 2005). The purpose of the written description requirement "is to ensure that the scope of the right to exclude ... does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification." Reiffin v. Microsoft Corp., 214 F.3d 1342, 1345-46 (Fed. Cir. 2000). The goal of the written description requirement is "to clearly convey the information that an applicant has invented the subject matter which is claimed." In re Barker, 559 F.2d 588, 592 n.4 (CCPA 1977) "A disclosure in an application, to be complete, must contain such description and details as to enable any person skilled in the art or science to which the invention pertains to make and use the invention as of its filing date." In re Glass, 492 F.2d 1228, 1232 (CCPA 1974).
The invention is, for purposes of the 'written description' inquiry, whatever is now claimed" (See page 1117). The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed" (See Vas-Cath at page 1116). The skilled artisan cannot envision the detailed chemical structure of the encompassed genus of polypeptides, and therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993).
The claims as amended are rejected under 102 and 103, see the rejections above. Applicant’s comments pertaining to the Nagase reference was considered but not deemed persuasive. The Nagase reference teach the recited yeast cell and method of producing ergothioneine as stated on the record. Thus, as the reference remains relevant the rejection remains. For these reasons the claimed invention is rejected, however, the examiner would welcome a conversation to reduce the remaining issues.
Conclusion
11. No claims are presently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HOPE A ROBINSON whose telephone number is (571)272-0957. The examiner can normally be reached 9-5pm, Monday- Friday.
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/HOPE A ROBINSON/Primary Examiner, Art Unit 1652