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: Election/Restrictions
Applicant's election with traverse of Group II, claims 34-35 in the reply filed on 05/08/2026 is acknowledged. Applicants’ election of Group II, claims 34-35 with traverse and the traversal is as follows: “Applicant traverses on the ground all groups are related by novel compositions of a three part system of the same components, namely a TYH capable of hydroxylating L-tyrosine and oxidizing L-DOPA; a 4,5-DOPA extradiol dioxygenase (DOD); and an enzyme having glycosyltransferase activity”.
The traversal by the applicants’ is answered as follows: Applicants’ arguments have been fully considered but are not deemed persuasive to withdraw the restriction requirement previously applied in the Office-action dated 02/11/2026; for details see 35 USC 103 rejection below. Thus, a comphrensive search of all inventions in Groups I-III would be a serious burden and contrary to applicants’ arguments, the requirement is still deemed proper and is therefore made FINAL. Amended Claims 22-41 are pending in this application, elected Group II, claims 34-35 reading on the elected invention is now under consideration for examination; non-elected claims 22-33 and 36-41 of Groups’ I and IIII are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 05/08/2026.
Priority
Acknowledgment is made of applicants’ claim for foreign priority under 35 U.S.C. 119(a)-(d). This application is a 371 of PCT/EP2022/064722 filed on 05/31/2022 and claims the priority date of EPO application 21176783.5 filed on 05/31/2021.
Information disclosure statement
The information disclosure statements (IDS) submitted on 02/26/2024, 01/07/2025, 04/28/2026 and 04/30/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS statements are considered and initialed by the examiner.
Objections to Abstract/Specification
I. The Abstract of the disclosure is objected to because, Abstract should be on a separate sheet of paper. The abstract of the disclosure is objected to because the abstract is presented as part of the first page of a WO publication. The abstract should be presented as a single sheet apart from all other bibliographic material including the information included on the first page of a WO publication. If EFS is used to submit a replacement abstract, the appropriate abstract (ABST) document code should be used for the one-page document. Correction is required. See MPEP § 608.01 (b).
II. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. The specification contains hyperlinks to various site domains, for example, pages 11 and 100-103 of the instant application. Applicants’ are required to thoroughly scrutinize the specification and delete all embedded hyperlink and/or other form of browser-executable code. See MPEP § 608.01. Appropriate correction is required.
III. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections: 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(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 34-35 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Claims 34-35 require a genus of yeast cells capable of producing one or more betalains, wherein said yeast cell comprises a genus of heterologous (TYH) capable of hydroxylating L-tyrosine and oxidizing L-DOPA, a genus of 4,5-DOPA extradiol dioxygenase (DOD) and a genus of glycosyltransferases including variants and mutants of unlimited and undefined structures, wherein said yeast cell comprises any undefined mutation resulting in reduced activity of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) and a method of producing betalain. The claims are not fully supported by the description. Again, a person skilled in the art would not know how to conduct the process/method according to the invention, since the description lacks information of genus of yeast cells capable of producing one or more betalains, wherein said yeast cell comprises a genus of heterologous (TYH) capable of hydroxylating L-tyrosine and oxidizing L-DOPA, a genus of 4,5-DOPA extradiol dioxygenase (DOD) and a genus of glycosyltransferases including variants and mutants of unlimited and undefined structures, wherein said yeast cell comprises any undefined mutation resulting in reduced activity of 4- hydroxyphenylpyruvate dioxygenase (4-HPPD) and a method of producing betalain and there is no evidence of possession of the entire genus in the claimed yeast. What is more, the determination of genus of polypeptides with associated function and structure requires excessive effort and undue experimentation. There is no guidance in the specification and the skilled person should not be left in any doubt as to which subject matter is covered and which is not. The skilled person should be able to establish the demarcation of the scope of the claim (i.e. its extent of protection) without undue burden.
To provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. Applicants are directed to MPEP § 2163 for guidelines on compliance with the written description requirement.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. For a broad generic claim, the specification must provide adequate written description to identify the genus of the claim.
“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 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (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.
MPEP § 2163 further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the biomolecule, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed biomolecule.”
“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 the applicant was in possession of the claimed genus.” MPEP 2163.
Furthermore, 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 disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure ‘indicates that the patentee has invented species sufficient to constitute the gen[us].’ 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.’). ‘A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.’ In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).” MPEP 2163.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. However, a showing of possession alone does not cure the lack of a written description. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 969-70, 63 USPQ2d 1609, 1617 (Fed. Cir. 2002). 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. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). See MPEP 2163(I).
The specification discloses and is limited to a few species in the claimed yeast and method i.e., the only embodiment shown in Examples 2-5, pages 92-94 of specification, provides evidence for betalain production, specific yeast strains that express defined structures: heterologous (TYH) capable of hydroxylating L-tyrosine and oxidizing L-DOPA, a 4,5-DOPA extradiol dioxygenase (DOD) and a glycosyltransferase, which is insufficient to put one of skill in the art in possession of the attributes and features of all species within the claimed a genus of yeast cells capable of producing one or more betalains, wherein said yeast cell comprises a genus of heterologous (TYH) capable of hydroxylating L-tyrosine and oxidizing L-DOPA, a genus of 4,5-DOPA extradiol dioxygenase (DOD) and a genus of glycosyltransferases including variants and mutants of unlimited and undefined structures, wherein said yeast cell comprises any undefined mutation resulting in reduced activity of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) and a method of producing betalain.
While generically the methods for producing betalain with specific structures and associated function is known, the structural and functional elements of the presently recited claims and in the instant method can vary substantially within the above given claimed recitations.
The art also teaches, even highly structurally homologous polypeptides do not necessarily share the same function and conversely functionally similar molecules do not necessarily have similar structures. For example proteins having similar structure have different activities; Witkowski et al., (Biochemistry 38:11643-11650, 1999) teaches that one conservative amino acid substitution transforms a b-ketoacyl synthase into a malonyl decarboxylase and completely eliminates b-ketoacyl synthase activity. Similarly, Wishart et al., (J. Biol. Chem., 1995, Vol. 270(10): 26782-26785) teach that a single mutation converts a novel phosphotyrosine binding domain into a dual-specificity phosphatase. 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.
Hence, the recited genera of polypeptides in the claimed yeast and method are interpreted to have widely variable structures, since minor changes may result in changes affecting function and no additional information correlating structure with function has been provided
Therefore, those of skill in the art would not accept that the inventor had been in possession of the full genus of yeast cells capable of producing one or more betalains, wherein said yeast cell comprises a genus of heterologous (TYH) capable of hydroxylating L-tyrosine and oxidizing L-DOPA, a genus of 4,5-DOPA extradiol dioxygenase (DOD) and a genus of glycosyltransferases including variants and mutants of unlimited and undefined structures, wherein said yeast cell comprises any undefined mutation resulting in reduced activity of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) and a method of producing betalain as claimed in the instant claims. The specification does not provide accurate experimental conditions of the of the claimed yeast and process and are not defined and it is not clear what is encompassed in the instant yeast and method claims for producing betalains.
Consequently, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus of yeast cells capable of producing one or more betalains, wherein said yeast cell comprises a genus of heterologous (TYH) capable of hydroxylating L-tyrosine and oxidizing L-DOPA, a genus of 4,5-DOPA extradiol dioxygenase (DOD) and a genus of glycosyltransferases including variants and mutants of unlimited and undefined structures, wherein said yeast cell comprises any undefined mutation resulting in reduced activity of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) and a method of producing betalain by the claimed yeast and method would meet the limitations of the claims.
Enablement
Claims 34-35 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 few species in the claimed yeast and method i.e., the only embodiment shown in Examples 2-5, pages 92-94 of specification, provides evidence for betalain production, specific yeast strains that express defined structures: heterologous (TYH) capable of hydroxylating L-tyrosine and oxidizing L-DOPA, a 4,5-DOPA extradiol dioxygenase (DOD) and a glycosyltransferase, and the specification does not reasonably provide enablement for genus of yeast cells capable of producing one or more betalains, wherein said yeast cell comprises a genus of heterologous (TYH) capable of hydroxylating L-tyrosine and oxidizing L-DOPA, a genus of 4,5-DOPA extradiol dioxygenase (DOD) and a genus of glycosyltransferases including variants and mutants of unlimited and undefined structures, wherein said yeast cell comprises any undefined mutation resulting in reduced activity of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) and a method of producing betalain. 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/use the invention commensurate in scope with these claims without undue experimentation.
Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 8 USPQ 2nd 1400 (Fed. Cir. 1988) as follows: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the 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 claim(s).
Claims 34-35, broadly encompass a genus of yeast cells capable of producing one or more betalains, wherein said yeast cell comprises a genus of heterologous (TYH) capable of hydroxylating L-tyrosine and oxidizing L-DOPA, a genus of 4,5-DOPA extradiol dioxygenase (DOD) and a genus of glycosyltransferases including variants and mutants of unlimited and undefined structures, wherein said yeast cell comprises any undefined mutation resulting in reduced activity of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) and a method of producing betalain.
The claims are broadly drawn to a genus of yeasts and a genus of polypeptides with the associated function encompassed by the claimed yeast and method would meet the limitations of the claims. There is no guidance regarding a genus of yeast cells capable of producing one or more betalains, wherein said yeast cell comprises a genus of heterologous (TYH) capable of hydroxylating L-tyrosine and oxidizing L-DOPA, a genus of 4,5-DOPA extradiol dioxygenase (DOD) and a genus of glycosyltransferases including variants and mutants of unlimited and undefined structures, wherein said yeast cell comprises any undefined mutation resulting in reduced activity of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) and a method of producing betalain nor guidance and nor are there any working examples of such. Thus, the scope of the claims is extremely broad compared to the guidance and exemplification provided in the specification. The scope of the claims must bear a reasonable correlation with the scope of enablement. See In re Fisher, 166 USPQ 19 24 (CCPA 1970).
Thus, the state of the art recognized that it would be highly unpredictable that wide variation in the structures associated with function and ability expressing the wide variety of structures in yeasts is challenging and requires optimization of various parameters. One of ordinary skill in the art could not predictably extrapolate the teachings in the specification to those with the claimed yeast and method.
In view of the great breadth of the claims, amount of experimentation required to make and use the claimed composition in the claimed method, the lack of guidance, working examples, and unpredictability of the art in predicting the use of the identified enzymes/polypeptides in claimed yeast and method of the present invention for the above purpose, the claimed invention would require undue experimentation. As such, the specification fails to teach one of ordinary skill how to use the full scope of the enzymes/polypeptides in the claimed yeast and method encompassed by the claims. Without sufficient guidance, determination of a genus of yeast cells capable of producing one or more betalains, wherein said yeast cell comprises a genus of heterologous (TYH) capable of hydroxylating L-tyrosine and oxidizing L-DOPA, a genus of 4,5-DOPA extradiol dioxygenase (DOD) and a genus of glycosyltransferases including variants and mutants of unlimited and undefined structures, wherein said yeast cell comprises any undefined mutation resulting in reduced activity of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) and a method of producing betalain is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly extensive and undue. See In re Wands (858 F.2d 731, 8 USPQ 2nd 1400 (Fed. Cir. 1988).
Claim Rejections: 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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.
Claims 34-35 are rejected under 35 U.S.C. 103(a) as being unpatentable over Mori et al., (US 12,241,102 B2; PCT Publication date 04/23/2020, filing date 10/18/2019) and further in view of Polturak et al., (PNAS., 2017, Vol. 114(34): 9062-9067), Wang et al., (Phytochem., 2016, Vol. 132: 16-25) and Larroude et al., (Microorganisms, 2021, Vol. 9, 838, pages 1-11).
Regarding claims 34-35, Mori et al., (US 12,241,102 B2; PCT Publication date 04/23/2020, filing date 10/18/2019) teach yeast cell capable of producing one or more betalains, said yeast cell expressing: a first heterologous enzyme (TYH) capable of hydroxylating L-tyrosine and oxidizing L-DOPA; b. a second heterologous enzyme which is a 4,5-DOPA extradiol dioxygenase (DOD); and C. a third heterologous enzyme having glycosyltransferase activity; whereby said cell is capable of producing one or more betalains, wherein said one or more betalains comprise one or more glycosylated betalains:
Mori et al., disclose a synthesis method for a betalain pigment, including: culturing a host that has been introduced therein the following gene encoding an amaranthin or gomphrenin-I-glucuronide synthetase, a gene encoding an enzyme having activity of hydroxylating a 3-position of a phenol ring of tyrosine, a gene encoding an enzyme having L-DOPA oxidase activity, a gene encoding an enzyme having activity of glycosylating a phenolic hydroxy group/glycosyltransferase, and a gene encoding an enzyme having DOPA 4,5-dioxygenase activity, and that has an ability to produce tyrosine or 3-hydroxy-L-tyrosine (L-DOPA), and extracting a betalain pigment from the host after the culturing (Abstract Fig. 1-3, reproduced below; and entire document);
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Mori et al., teach “The host to be used in the synthesis method for a betalain pigment of the present invention is not particularly limited, as long as the host has an ability to produce tyrosine or 3-hydroxy-L-tyrosine. For example, there may be used a synthesis system known per se, such as a recombinant Escherichia coli protein synthesis system, an insect protein synthesis system, a yeast protein synthesis system, a plant cell protein synthesis system, a cell-free protein synthesis system, a plant protein synthesis system, or animal cultured cells” (Col. 18, lines 28-38).
However, Mori et al., (US 12,241,102 B2; PCT Publication date 04/23/2020, filing date 10/18/2019) is silent regarding and wherein said yeast cell comprises a mutation resulting in reduced activity of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD; as in claim 34).
Regarding claims 34-35, Polturak et al., (PNAS., 2017, Vol. 114(34): 9062-9067) also teach a method for producing one or more betalains/biosynthetic pathway, expression of three genes comprising a first heterologous enzyme (TYH) capable of hydroxylating L-tyrosine and oxidizing L-DOPA; b. a second heterologous enzyme which is a 4,5-DOPA extradiol dioxygenase (DOD); and C. a third heterologous enzyme having glycosyltransferase activity (Abstract; col. 2, ¶ 2, page 9062; Fig. 1, page 9063; Fig. 4A, page 9065; and entire document).
Regarding claim 34, i.e., yeast cell comprises a mutation resulting in reduced activity of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) the following references via different lines of evidence provide teaching, suggestion and motivation to reduce/eliminate the activity of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) in a host cell engineered to produce betalains for the following reasons:
Wang et al., (Phytochem., 2016, Vol. 132: 16-25) provide teaching, suggestion and motivation to reduce/eliminate the activity of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD), as 4-HPPD is involved in directing the carbon flow 4-hydroxyphenylpyurvate (4-HPP) towards unwanted by-product/pigment homogentisate (see Abstract; Fig. 1, page 17); and 4-hydroxyphenylpyurvate (4-HPP) is an intermediate necessary for the production of betalain (Fig. 1, page 17), and therefore a skilled artisan would be motivated to reduce the activity of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) to increase the production of betalain.
Larroude et al., (Microorganisms, 2021, Vol. 9, 838, pages 1-11) also provide teaching, suggestion and motivation to reduce/eliminate the activity of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD), as 4-HPPD is involved in directing the carbon flow 4-hydroxyphenylpyurvate (4-HPP) towards unwanted by-product/pigment homogentisate (see Abstract; Fig. 1, page 2) and provide evidence in a yeast cell/ Yarrowia lipolytica deletion of hydroxyphenylpyruvate dioxygenase (4-HPPD) resulted in elimination of by-product/pigment homogentisate (Table 1, DJMY8131 strain Yarrowia lipolytica deletion of hydroxyphenylpyruvate dioxygenase (4-HPPD), Fig. 4, page 11).
Hence, a skilled artisan will be motivated to reduce the activity of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD), said metabolic engineering in yeast involves the modification of endogenous biosynthetic pathways to increase the biosynthesis of target bioactive compounds/betalain, reduce the production of an unwanted compound/homogentisate or other metabolites and unwanted pigments. A skilled artisan will be motivated in a single step modification of a biosynthetic pathway or competitive pathways blocked to divert metabolic flow towards betalain formation. The identification of the genes encoding enzymes involved in the betalain biosynthetic pathway by Mori et al., and Polturak et al., will motivate the skilled artisan for the development of metabolic engineering strategies to increase betalain production by reducing/eliminating the activity of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) as described in references of Wang et al., and Larroude et al.
As such, disclosure of strategy and methods including structural and functional elements for a method of producing betalain in the claimed yeast and process, such as that of references of Mori et al., Polturak et al., Wang et al., and Larroude et al., teaching the advantages of said modifications, and clearly suggests to a skilled artisan to modify the teachings of Mori et al., and Polturak et al., and a skilled artisan would be motivated to incorporate the structural and functional elements of the cited secondary references of Wang et al., and Larroude et al., in the claimed yeast and process, and the combined references also provide the advantages of modifying the primary teachings of Mori et al., by incorporating the structural and functional elements of secondary references as claimed in the instant invention and is well known in the art (for details see the rejection above).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claimed process, as suggested by Mori et al., Polturak et al., Wang et al., and Larroude et al. A person of ordinary skill in the art is motivated to make such change depending on the experimental need i.e., yeast cell capable of producing one or more betalains, said yeast cell expressing: a. a first heterologous enzyme (TYH) capable of hydroxylating L-tyrosine and oxidizing L-DOPA; b. a second heterologous enzyme which is a 4,5-DOPA extradiol dioxygenase (DOD); and C. a third heterologous enzyme having glycosyltransferase activity; whereby said cell is capable of producing one or more betalains, wherein said one or more betalains comprise one or more glycosylated betalains, and wherein said yeast cell comprises a mutation resulting in reduced activity of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) (as in claims 34-35), because a skilled artisan would realize such a modification would be useful to efficiently produce betalain in the claimed process. One of ordinary skill in the art has a reasonable expectation of success at adding the steps in the claimed yeast and process, as suggested in the teachings of Polturak et al., Wang et al., and Larroude et al., and are well known in the art. Therefore, the invention as a whole lack an inventive step over the prior art. The expectation of success is high, because the combined teachings of Mori et al., Polturak et al., Wang et al., and Larroude et al., also provide the structural and functional elements of the instant invention (Teaching, Suggestion and Motivation).
Given this extensive teaching in prior art (Mori et al., Polturak et al., Wang et al., and Larroude et al.,) the claimed yeast and process, as taught by the instant invention and as claimed in claims 34-35 is not of innovation but of ordinary skill in the art and the expectation of success is extremely high i.e., “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103.”KSR, 550 U.S. at, 82 USPQ2d at 1397”.
Hence, claims 34-35 are rejected under 35 U.S.C. 103(a) as being unpatentable over Mori et al., (US 12,241,102 B2; PCT Publication date 04/23/2020, filing date 10/18/2019) and further in view of Polturak et al., (PNAS., 2017, Vol. 114(34): 9062-9067), Wang et al., (Phytochem., 2016, Vol. 132: 16-25) and Larroude et al., (Microorganisms, 2021, Vol. 9, 838, pages 1-11).
Allowable Subject Matter/Conclusion
None of the claims are allowable.
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/GANAPATHIRAMA RAGHU/ Primary Examiner, Art Unit 1652
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