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 .
Claim Interpretation
The specification on pages 5-6 sets forth a definition of “manufacture” setting forth in part:
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Reference to host cells is exemplary only as is not limiting to the definition of “manufacture.” As such, the method of claim 17 includes performance in vitro or performance in situ in a naturally-occurring organism.
The specification contains no specific definition of “fragment.” However, a fragment of an amino acid sequence exhibiting diterpene alcohol synthase activity is understood to be a contiguous sequence of an amino acid sequence as otherwise embodying an amino acid sequence as recited in claims a) to d) that is in itself sufficient for diterpene alcohol synthase.
Election/Restrictions
Applicant’s election of Invention I (claims 27-22 and 31) and species of SEQ ID NO: 4 (diterpene alcohol synthase), sclareol, a host cell and maltose binding protein (fusion protein) in the reply filed on 07/01/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim 32 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/01/2026.
Claims 19 and 25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/01/2026. Claims 19 and 25 are directed towards the unelected species of abienol.
In the interest of compact prosecution, claims 23-24 and 26-30 are not withdrawn and are examined herein. It is noted that the species elections remain of record. In addition to the reasons for lack of unity of invention stated in the prior office action, the rejection of at least claim 23 under 35 U.S.C. 102(a)(1) below is noted below and incorporated herein by reference as additional reasons why the claims (and particularly species) do not all require a common special technical feature making a contribution over the prior art.
In view of the withdrawal of the restriction requirement between Groups I and II, 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.
Drawings
The drawings are objected to because Fig. 4 shows amino acid sequences without providing a Sequence Identifier including in the brief description of the drawings. See 37 CFR 1.831(c).
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 17, 18, 23, and 24 objected to because of the following informalities:
The claim language in part a) of the claims being “an amino acid sequence as shown in SEQ ID NO:” 3, 4, 5, 6, 7, 8, 9, 10, or 34 is understood as requiring the full-length of one of the recited Sequence Identifiers. However, it is recommended that the claims be placed in better format by reciting “an amino acid sequence comprising” one of the Sequence Identifiers. Similarly for recitation in of nucleic acid sequences in part c of the claims, it is recommended claims be amended to recite “a nucleic acid sequence comprising” one of the Sequence Identifiers.
Appropriate correction is required.
Specification
The disclosure is objected to because of the following informalities:
MPEP 2422.03(I) provides the following:
The Office strongly suggests filing the sequence listing required by 37 CFR 1.821(c) as a text file via EFS-Web. If a new application is filed via EFS-Web with an ASCII text file sequence listing that complies with the requirements of 37 CFR 1.824(a)(2) -(6) and (b), and applicant has not filed a sequence listing in a PDF file, the text file will serve as both the paper copy required by 37 CFR 1.821(c) and the computer readable form (CRF) required by 37 CFR 1.821(e). Note that the specification must contain a statement in a separate paragraph that incorporates by reference the material in the ASCII text file identifying the name of the ASCII text file, the date of creation, and the size of the ASCII text file in bytes. See MPEP § 2422.03(a) for additional information pertaining to EFS-Web submission of sequence listings.
The electronic file wrapper contains a Sequence Listing filed as a text file submitted on 01/05/2024; however, the required statement indicated above cannot be found in the specification.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 31 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because of the following.
“"Use" claims that do not purport to claim a process, machine, manufacture, or composition of matter fail to comply with 35 U.S.C. 101.” MPEP 2173.05(q). Claim 21 recites such a use claim and does not comply with 35 U.S.C. 101.
Claim Rejections - 35 USC § 112
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 31 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.
“It is appropriate to reject a claim that recites a use but fails to recite steps under 35 U.S.C. 101 and 35 U.S.C. 112(b) if the facts support both rejections.” MPEP 2173.05(q). The rejection under 35 U.S.C. 101 above is incorporated herein by reference. Since claim 31 fails to recite a statutory category and it is unclear what acts in terms of forming a process or a composition would infringe claim 31, an ordinarily skilled artisan is unable to understand how to avoid infringement.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 22 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 22 depends from claim 17. "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." MPEP 2113(I). Recitation of “manool, sclareol and/or abienol obtainable by the method of clam 17” is a product-by-process limitation. As such, claim 22 does not require the performance of any method step that is a positive limitation of claim 17. Manool, sclareol and/or abienol have the same identical chemical structure regardless of how the same is produced. For example, the specification, Table 1, discloses production of sclareol by the activity of SsSS (sclareol synthase from Salvia sclarea) that is understood not to meet the features of a polypeptide exhibiting diterpene alcohol synthase as recited in claim 17 but forms a sclareol compound having the same structure.
As such, an embodiment of claim 17 can be made by forming a composition by combining a host cell comprising a polypeptide exhibiting diterpene alcohol synthase as recited in claim 17 and sclareol obtained by the activity of SsSS or extracted from a plant source without performing any of the method steps of claim 17. As such, claim 22 fails to include all the limitations of claim 17 from which claim 22 depends, the omitted limitations being the method steps of claim 17.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 17-18, 20-24 and 26-31 (all non-withdrawn claims) 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 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., 119, F.3d 1559, 1568, 43 USPQ2d 1398, 1405 (Fed. Cir. 1997).
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(II)(3)(a).
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(II)(3)(a).
Scope of claims
The claims recite a genus of polypeptides having “diterpene alcohol synthase activity” particularly converting CPP or LPP into manool, sclareol and/or abienol having at least 60% identity to one of SEQ ID NO: 3, 4, 5, 6, 8, 9, 10 or 34 (herein, the “Sequence Identifiers” when referenced as a group) or encoded by a nucleic acid with at least 60% identity to one of SEQ ID NOS: 1, 2, 16, 17, 18 or 35. Such activity is understood as a form of terpene synthase, diterpene synthase or sesquiterpene synthase activity. See Specification, page 37, lines 1-5.
Analysis
Polypeptides falling within the recited genes are required to have activity to form manool, sclareol and/or abienol from CPP or LPP, as appropriate. The claims directly allow for 40% (i.e. 60% identity) of the recited Sequence Identifiers to vary. Further, since base changes can be distributed across codons (rather than concentrated in a small number of codons), a polypeptide encoded by a nucleic acid with at least 60% identity to one of SEQ ID NOS: 1, 2, 16, 17, 18 or 35 can have significantly less than 60% identity to any of SEQ ID NO: 3, 4, 5, 6, 8, 9, 10 or 34. As such, there is substantial structural variation within the genus recited.
It is well established in the art that the amino acid sequence of terpene synthases is minimally predictive of products produced. Degenhardt et al. (Monoterpene and sesquiterpene synthases and the origin of terpene skeletal diversity in plants, Phytochemistry 70, 2009, 1621-37), page 1628, right col, evidences: Despite our detailed knowledge of monoterpene and sesquiterpene synthase mechanisms, comparatively little information is available about how various structural features of the proteins themselves mediate substrate binding and catalysis. Even though there is a substantial degree of amino acid sequence similarity among plant monoterpene and sesquiterpene synthases, similarity is based more on taxonomic affinities of the plant species from which the gene was isolated rather than the type of products formed.
For example, GenBank, Accession No. KT588489, 2016, www.ncbi.nlm.nih.gov, discloses a diterpene synthase from Taiwania cryptomerioides described as a ent-kaur-16-ene synthase and having about 70% identity to SEQ ID NO: 6 without apparent ability to form manool, sclareol and/or abienol. Ma et al. (Biochemical characterization of diterpene synthases of Taiwania cryptomerioides expands the known functional space of specialized diterpene metabolism in gymnosperms, Plant J. 100, 2019, 1254-72) (see IDS), Fig. 1, describes the same enzyme (TcKSL8) as converting ent-CPP to ent-kaurene.
“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.” “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.”
Based upon the evidence above, even when presented with a polypeptide having the recited percent identity to one of the Sequence Identifiers (or encoded by a nucleic acid sequence with at least 60% identity to one of SEQ ID NOS: 1, 2, 16, 17, 18 or 35) that has some form of terpene synthase activity, an ordinarily skilled artisan cannot predict the operability of such enzyme to form manool, sclareol and/or abienol as required by the claims and recited genus of polypeptide with diterpene alcohol synthase activity. The specification contains a discussion of regions of Cup2v1, Cup2v2a and Cup2v2b proteins that may be functionally related to product determination. See Specification Fig. 4. However, “This region in the synthases is located at a location corresponding to the product determining region of other synthases but different from the product determining region of said other synthases including the product determining region in the known Salvia sclareol synthase. Although Cup2v1, Cup2v2a and Cup2v2b have different product specificity (see below), the region typically responsible for determining product specificity in other diterpene synthases known is very different yet conserved between said Cup proteins.” Specification, page 38. The claims do not require the discussed region conserved between Cup proteins to be maintained in embodiment diterpene alcohol synthase polypeptides and the specification admits that other synthases forming recited products (e.g. known Salvia sclareol synthase) do not have the conserved regions of Cup proteins as discussed. That is, the recited genus of diterpene alcohol synthases does not require the specific presence of structure known to produce specific products wherein multiple unrelated sequences can produce the same product and includes other, non-disclosed structures. Further, it is unclear if even if the regions depicted in Fig. 4 of the specification were to be conserved that product specificity would be maintained if large differences (e.g. mutation of up to 40% of amino acid residues, or more) were introduced into any of SEQ ID NOS: 3, 4, 5, 6, 8, 9, 10 or 34.
As such, the specification lacks a sufficient description of shared characteristics that allows for the identification of synthases that specifically form manool, sclareol and/or abienol apart from other active terpene synthases that do not (e.g. the synthase of GenBank KT588489) or polypeptides with no activity. While it is recognized that the specification, pages 36-37, describes identification of putative synthases from C. gigantea by homology, it was prior known that C. gigantea produces manool such that a terpene synthase forming the same was known to be present. The same description does not allow for prediction of other synthases producing manool, sclareol and/or abienol with the recited sequence identity from other sources based on the disclosure of the specification.
Further, the specification, page 40, describes Cup2v1 (SEQ ID NO: 3) as forming abienol, Cup2v2a (SEQ ID NO: 4) as forming manool and sclareol and Cup2v2b (SEQ ID NO: 34) as forming sclareol. As such, even though such enzymes were identified from C. gigantea by homology, the specification indicates that the same is insufficient to allow for the identification of specific products formed cannot be predicted by homology. Although Cup2v1 and Cup2v2a share over 93% identity (specification, page 38), the same polypeptides from different products.
For these reason, the specification does not provide for an adequate written description to allow for prediction of operability in the invention of any species other than the one disclosed and by extension does not provide for an adequate written description for a genus of all polypeptides with activity to form manool, sclareol and/or abienol with structural diversity that includes polypeptides with 60% (or even less) identity to any of SEQ ID NO: 3, 4, 5, 6, 8, 9, 10 or 34. Further, the claims should indicate the specific product formed by a polypeptide with identity to specific Sequence Identifiers.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 17, 18, 20, 23, 24 and 27 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhou et al. (In-depth transcriptome characterization uncovers distinct gene family expansions for Cupressus gigantea important to this long-lived species’ adaptability to environmental cues, BMC Genomics 20, 2019, 213) as evidenced by Dickschat et al. (Bacterial Diterpene Biosynthesis, Angew. Chem. Int. Ed. 58, 2019, 15964-76) and Uniprot, Accession No. J9QS23, 2020, www.uniprot.org.
Specification, page 36, describes the following:
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Example 1 of the specification further explains that Cup2v (SEQ ID NO: 3), Cup2v2a (SEQ ID NO: 34) and Cup2v2b (SEQ ID NO: 4) were cloned from RNA extracted from C. gigantea.
The specification, page 1, describes that CPP is converted to manool and the specification, page 40, indicates that a polypeptide with recited SEQ ID NO: 34 has activity to convert CPP to manool.
The specification, page 2, describes “Diterpene biosynthesis starts from geranylgeranyl pyrophosphate (GGPP)” and “Starting from GGPP, diterpene biosynthesis is usually mediated by two steps: Step 1 towards a cyclized diphosphate (e.g. labda-13-en-8-ol diphosphate or LPP, copalyl-PP or CPP), and step 2 for converting this substrate to the final product.”
“"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." MPEP 2112(I). “There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference.” MPEP 2112(II).
Claim 17 does not require any active step to be performed in vitro or with a purified enzyme nor for any produced C-20 terpenoid alcohol to be purified. As such, claim 17 reads on the step of converting GPP to CPP and converting CPP to manool using a diterpene alcohol synthase having recited SEQ ID NO: 34 performed in vivo in a C. gigantea plant by operation of its normal metabolism.
"In relying upon the theory of inherency, the examiner must provide a basis in fact and/or technical reasoning to reasonably support the determination that the allegedly inherent characteristic necessarily flows from the teachings of the applied prior art." MPEP 2112(IV). Here, the specification evidences that manool is produced from CPP and that C. gigantea both expresses a polypeptide having SEQ ID NO: 34 and produces manool. The same provides from a basis in fact and/or technical reasoning to reasonably support the determination that C. gigantea undergoing its ordinary growth and metabolism in its native environment performs the following method:
A method for the manufacture of at least one C-20 terpenoid alcohol comprising the steps of:
a) converting geranylgeranyl pyrophosphate into copalyl diphosphate (CPP); and
b) converting CPP into at least one C-20 terpenoid alcohol being manool, wherein said conversion is carried out by a polypeptide exhibiting diterpene alcohol synthase activity having recited SEQ ID NO: 34 or having at least 60% identity to recited SEQ ID NO: 34.
That is, the evidence of record reasonably supports that C. gigantea produces GPP that is converted to CPP and CPP converted to manool by action of a diterpene alcohol synthase having recited SEQ ID NO: 34 as part of its natural metabolism in the absence of any artificial intervention. Since C. gigantea is known in the prior art (see Zhou below), the naturally-occurring C. gigantea plant performs and anticipates the methods of claims 17 and 18 and use of claim 31 through its natural metabolism.
Zhou evidences that Cupressus gigantea is known in the prior art and is described as producing terpenes. “Here, metabolic pathway of the terpenoid backbone biosynthesis for the unigenes identified in C. gigantea is shown in Additional file 12: Figure S6.” Zhou, page 3, right col. Figure S6 of Zhou show that the metabolism of C. gigantea through products and intermediates of glycolysis produces geranylgeranyl-PP (GGPP) that is used for diterpenoid biosynthesis. Zhou is silent regarding production of CPP from GGP and conversion of CPP to manool using a polypeptide having SEQ ID NO: 34. However, However, Table S5 (contig_4303) of Zhou evidences that C. gigantea expresses at least one copalyl diphosphate synthase (see on-line information in Zhou) excerpted below. The specification evidences that C. gigantea expresses a polypeptide having recited SEQ ID NO: 34 and that C. gigantea converts GGPP to CPP wherein CPP is converted to manool by activity of a peptide having recited SEQ ID NO: 34 as to meet the features of claim 17 and 18.
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Regarding claims 23, 24, and 27, claims 23 and 24 do not require the polypeptide to be isolated or purified in any way. As such, a naturally-occurring C. gigantea tree in its native environment anticipates claims 23 and 24. Regarding claim 27, a polynucleotide as recited in claim 27, the chromosomes of C. gigantea is a polynucleotide as well as RNA produced by C. gigantea. As discussed above, the specification states that C. gigantea produces an RNA/polynucleotide encoding a polynucleotide encoding SEQ ID NO: 34.
Regarding claim 20, as discussed, the specification evidences the metabolism of C. gigantea converts GGPP to CPP. As discussed, Zhou, Table S5 evidences that C. gigantea expresses a copalyl diphosphate synthase, which is an enzyme activity that by definition converts GGPP to CPP. Zhou does not disclose the sequence of the copaly diphosphate synthase describe but states the same has about 40% identity to Uniprot J9QS23. Uniprot J9QS23 evidences that a copalyl diphosphate synthase has activity to convert GPP to CPP (EC 5.5.1.12) and has a “Asp-Xaa-Asp-Asp (DXDD) motif is important for the catalytic activity.” Dickschat, page 15971, evidences “To initiate a cationic cyclisation cascade, substrate ionization by type II DTSs is promoted by protonation through the action of the central aspartate group in a highly conserved DXDD motif. In general, four types of cyclisation reactions are known that lead to stereoisomeric variants of the labdane skeleton (Scheme 13). The chair–chair fold of GGPP may lead to CPP+, the direct precursor of copalyl diphosphate.” As such, the evidence of record supports that a copaly diphosphate synthase is a type II diterpene synthase that is further supported by Zhou describing that the copaly diphosphate synthase in Table S5 discussed above has identity to a copaly diphosphate synthase having the conserved DXDD motif of a type II diterpene synthase.
This rejection may be obviated by amending the claims to require a heterologous host cell or an in vitro process.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 17, 18, 20, 23, 24 and 27 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more. The claim(s) recite(s) a naturally-occurring protein/enzyme (or encoding nucleic acid) and method steps of the metabolism of C. gigantea that are both products of nature. This judicial exception is not integrated into a practical application because the claims do not recite additional steps or features that integrate into a practical application, as set forth in more detail below. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims do not recite additional steps or features as set forth in more detail below.
The rejections under 35 U.S.C. 102 set forth above are incorporated herein by reference.
Regarding claims 23, 24 and 27, the following is noted:
MPEP 2106(III) directs that claims drawn to 1) a composition of matter (step 1), 2) a law of nature or a natural phenomenon or a product of nature (step 2A) and 3) lacking recitation of additional elements that make the claims directed to significantly more than a judicial exception (step 2B) are ineligible for patenting under 35 U.S.C. 101. See MPEP 2106(III), flow chart. Step 2A into two prongs as set forth in MPEP 2106.04(II)(A).
“If the claim includes a nature-based product that does not exhibit markedly different characteristics from its naturally occurring counterpart in its natural state, then the claim recites a "product of nature" exception, and requires further analysis in Step 2A Prong Two to determine whether the claim as a whole integrates the exception into a practical application.” MPEP 2106.04(c). “It is important to keep in mind that product of nature exceptions include both naturally occurring products and non-naturally occurring products that lack markedly different characteristics from any naturally occurring counterpart.” MPEP 2106.04(b)(II).
“The markedly different characteristics analysis is part of Step 2A Prong One, because the courts use this analysis to identify product of nature exceptions.” MPEP 2106.04(c). “The markedly different characteristics analysis compares the nature-based product limitation to its naturally occurring counterpart in its natural state. Markedly different characteristics can be expressed as the product’s structure, function, and/or other properties, and are evaluated based on what is recited in the claim on a case-by-case basis. If the analysis indicates that a nature-based product limitation does not exhibit markedly different characteristics, then that limitation is a product of nature exception. If the analysis indicates that a nature-based product limitation does have markedly different characteristics, then that limitation is not a product of nature exception.” MPEP 2106.04(c)(II).
Examiners should keep in mind that if the nature-based product limitation is naturally occurring, there is no need to perform the markedly different characteristics analysis because the limitation is by definition directed to a naturally occurring product and thus falls under the product of nature exception.” MPEP 2106.04(c)(I).
Claims 23, 24 and 27 are directed towards a composition of matter such that step 1 is yes. As discussed above, the specification states that a diterpene alcohol synthase polypeptide having at least SEQ ID NO: 34 is encoded by an RNA (polynucleotide) produced by C. gigantea such that both the diterpene alcohol synthase polypeptide having SEQ ID NO: 34 and its encoding RNA are products of nature and as such do not have markedly different characteristics with respect to their naturally-occurring counterparts. Examiners should keep in mind that if the nature-based product limitation is naturally occurring, there is no need to perform the markedly different characteristics analysis because the limitation is by definition directed to a naturally occurring product and thus falls under the product of nature exception.” MPEP 2106.04(c)(I). As such, step 2A (prong 1) does not favor patentability.
For step 2A (prong 2), , “Prong Two asks does the claim recite additional elements that integrate the judicial exception into a practical application? In Prong Two, examiners evaluate whether the claim as a whole integrates the exception into a practical application of that exception.” MPEP 2106(II)(A)(2). Here, at least claims 23, 24 and 27 do not recite any additional claims elements. Similarly, Step 2B asks: Does the claim recite additional elements that amount to significantly more than the judicial exception”? MPEP 2106.05(II). As just discussed, claims 23, 24 and 27-28 lack any additional elements besides the nature-based product itself such that Step 2B does not favor patentability.
Regarding claims 17, 18, and 20, the following from MPEP 2106 2106.04(I)(C) is noted:
“For a process claim, the general rule is that the claim is not subject to the markedly different analysis for nature-based products used in the process. This is because the analysis of a process claim should focus on the active steps of the process rather than the products used in those steps. . . . However, in the limited situation where a process claim reciting a nature-based product is drafted in such a way that there is no difference in substance from a product claim, the claim is subject to the markedly different analysis for the recited nature-based product. These types of claims are drafted in a way that focuses on the product rather than the process steps. For example, consider a claim that recites, in its entirety, "a method of providing an apple." Under the broadest reasonable interpretation, this claim is focused on the apple fruit itself, which is a nature-based product. Similarly, claims to detecting naturally occurring cell-free fetal DNA (cffDNA) in maternal blood were held to be directed to the cffDNA, because the "existence and location of cffDNA is a natural phenomenon [and thus] identifying its presence was merely claiming the natural phenomena itself." Rapid Litig. Mgmt., 827 F.3d at 1048, 119 USPQ2d at 1374, (explaining the holding in Ariosa Diagnostics, Inc. v. Sequenom, 788 F.3d 1371, 115 USPQ2d 1152 (Fed. Cir. 2015)).”
Claims 17, 18 and 20 are analogous to the claims discussed in the holding in Rapid Litig. Mgmt. As discussed above, a C. gigantea undergoing its natural metabolism performs all of the method steps of claims 17, 18 and 20. As such, claims 17, 18 and 20 are claiming the natural phenomenon itself of C. gigantea having a metabolic pathway for producing manool that converts GGPP to CPP by activity of a type II diterpene synthase and converts CPP to manool by activity of a diterpene alcohol synthase having SEQ ID NO: 34. Again, claims 17, 18 and 20 do not require any process be performed in vitro and as indicated in claim 21 include steps carried out in a living cell. As such, claims 17, 18 and 20 encompass a process carried out in the naturally-occurring cells of C. gigantea as such, there is no markedly different characteristic difference between the recited claims and a naturally-occurring C. gigantea plant carrying a method meeting the methods of claims 17, 18 and 20 with regards to step 2A (prong 1).
For Step 2A (prong 2) and Step 2B, the claims do not recite any additional steps or elements that are not carried out by a C. gigantea plant as part of its natural metabolism. For example, these steps may be satisfied in favor of patentabilty if an additional step such as “collecting the manool, sclareol or abienol were recited,” but not such additional step is recited to establish a practical application or additional elements that amount to significantly more than the judicial exception such that Step 2A (prong 2) and Step 2B are not resolved in favor of patentability.
The rejection of claims 17, 18 and 20 may be obviated by amending the claims to require a heterologous host cell or an in vitro process.
Statement regarding prior art
The closest prior art is Zhou et al. (In-depth transcriptome characterization uncovers distinct gene family expansions for Cupressus gigantea important to this long-lived species’ adaptability to environmental cues, BMC Genomics 20, 2019, 213).
Zhou, abstract, states:
Cupressus gigantea, a rare and endangered tree species with remarkable medicinal value, is endemic to the Tibetan Plateau. Yet, little is known about the underlying genetics of the unique ecological adaptability of this extremely long-lived conifer with a large genome size. Here, we present its first de novo and multi-tissue transcriptome in-depth characterization.
We performed Illumina paired-end sequencing and RNA libraries assembly derived from terminal buds, male and female strobili, biennial leaves, and cambium tissues taken from adult C. gigantea. In total, large-scale high-quality reads were assembled into 101,092 unigenes, with an average sequence length of 1029 bp, and 6848 unigenes (6.77%) were mapped against the KEGG databases to identify 292 pathways. A core set of 41,373 genes belonging to 2412 orthologous gene families shared between C. gigantea and nine other plants was revealed. In addition, we identified 2515 small to larger-size gene families containing in total 9223 genes specific to C. gigantea, and enriched for gene ontologies relating to biotic interactions. We identified an important terpene synthases gene family expansion with its 121 putative members.
Among the unigenes characterized were specifically 121 terpene synthase genes. The short read sequences generated are deposited in GenBank under project Accession No. SRX2996533. However, the assembled gene or cDNA or contig sequences are not directly reported. That is, identification of the 121 putative terpene synthase unigenes would require repetition of the assembly work performed by the authors of Zhou. “Next, de novo assembly using Trinity produced a total of 135,542 contigs (103,584,408 bp in total, with mean length being 764 bp and with 18,728 bp the longest read length (Additional file 3: Table S1). These contigs (ordered sequences) were then joined into scaffolds. Subsequently, 102,553 scaffolds (104,432,740 bp in total length) were obtained, with a mean length of 1018 bp and the longest length being 23,390 bp. Subsequently, we extracted unigenes from the assembly obtained with Trinity. A total of 101,092 unigenes (104,109,640 bp) were obtained, the average length was 1029 bp with the longest being 25,331 bp.” Zhou, pages 2-3.
As such, it is unknown if terpene synthase genes encoding any of the recited Sequence Identifiers were identified by Zhou and recognized as a terpene synthase gene, since Zhou do not disclose the unigene or contig sequences assembled. That is, GenBank SRX2996533 is a large collection of 100 overlapping nucleotide sequence that requires an extensive amount of computation work to analyze to identify. A blast search of SEQ ID NO: 1 against GenBank SRX2996533 was performed, see Office Action Appendix. While hits were identified, the same is not a disclosure of a specific contig sequence being SEQ ID NO: 1 and its identification as a terpene synthase.
Conclusion
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/TODD M EPSTEIN/Primary Examiner, Art Unit 1652
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