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 Objections
Claim 11 is objected to for the following informalities:
In claim 11, line 1, “strain” is misspelled “train.”
Appropriate correction is required.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 365(c) or 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Korean Application No. 10-2021-0073669, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
The rejections of claim 7 under 35 U.S.C. 112(a) for lack of written description below are incorporated herein by reference. Just as the specification does not support a method of producing a genus of generic lichen-derived metabolites, the specification of Korean Application No. 10-2021-0073669 fails to provide an adequate written description for the same reasons. As such, claim 7 at this time is not entitled to the priority date of Korean Application No. 10-2021-0073669. It is noted that no certified translation of Korean Application No. 10-2022-0059678 is filed.
Drawings
The drawings are objected to because:
Figure 5 shows very small text on top of shaded background that is not legible.
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 Interpretation
Regarding claim 9, specification, para. [00178], states: Finally, the present inventors generated a strain expressing the three genes, the atr1, atr2 and atr3. The production of atranorin (Compound 5) was confirmed by MS/MS spectral matching with the reference spectrum of atranorin in the Lichen Database.
Since strain KACC 83048BP is described as producing atranorin, it is understood as expressing all of atr1 (SEQ ID NO: 1), atr2 (SEQ ID NO: 3) and atr3 (SEQ ID NO: 5) and this interpretation is applied below including for rejections under 35 U.S.C. 112(d). If this interpretation is incorrection, applicant is requested to clarify the structure of strain KACC 83048BP.
Claim Rejections - 35 USC § 112
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.
Claims 2, 5, 10 and 11 are 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 2 depends from claim 1. The structure of a gene being SEQ ID NO: 1, 3 or 5 as recited in claim 1 is unaffected nor modified by a requirement that the “gene is derived from a lichen” as recited in claim 2. The best understanding of claim 2 is the recitation of a product-by-process; however, "[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). A gene being an atranorin biosynthesis gene being SEQ ID NO: 1, 3 or 5 is unaffected by its method of manufacture. In order for claim 2 to further limit the subject matter of claim 1, there must be some embodiment that would infringe claim 1 but not infringe claim 2. However, no such embodiment exists since an atranorin biosynthesis gene being SEQ ID NO: 1, 3 or 5 that is not derived from a lichen infringes both claims 1 and 2 since the “patentability of a product does not depend on its method of production.”
Claim 5 depends from claim 4. “[T]he body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.” Claim 4 recites an intended use in the preamble thereof being “for producing a lichen-derived metabolite.” Further dependent claim 5 further defines the intended use recited in the preamble of claim 4 as the metabolite being a Markush group of specific compounds as recited. However, claim 4 in the body thereof fully sets forth all of the limitations of the claimed invention wherein a further recitation of the intended use of the vector of claim 4 “is not considered a limitation and is of no significance to claim construction.” As such, claim 5 that merely further defines the intended use recited in claim 4 does not further limit the subject matter of claim 4, or stated in other words, there is no embodiment of claim 4 that does not also infringe claim 5.
Claim 10 depends from 9. “[T]he body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.”
“The following types of claim language may raise a question as to its limiting effect:
(A) statements of intended use or field of use [anywhere in the claim], including statements of purpose or intended use in the preamble.” MPEP 2103(I)(C).
Claim 10, as its only claim feature, recites an intended use of the strain recited in claim 9 “for producing atranorin.” Claim 9 fully sets forth all structure of a strain and any further recitation of intended use, whether presented in a preamble or in a body of a claim, “is not considered a limitation and is of no significance to claim construction” such that claim 10 does not further limit the subject matter of claim 9.
Claim 11 depends from claim 9. The strain of claim 9 is understood to comprise all of SEQ ID NOS: 1, 3 and 5 which are described to be necessary for production of atranorin in a A. rabiei strain. As such, claim 11 only restates structure already required by claim 9 such that claim 11 does not further limit the subject matter of claim 9.
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 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 3 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3 recites the limitation "the lichen" in line 1. There is insufficient antecedent basis for this limitation in the claim. There is no recitation in claim 1 of any claim feature that provides a literal nor a reasonable antecedent basis for “the lichen” such that it is unclear as to what claim feature is referenced.
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 9-12 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
An “analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention.” MPEP 2164.01. “A conclusion of lack of enablement means that . . . the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention [i.e. commensurate scope] without undue experimentation.” In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); MPEP 2164.01.
In In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir. 1988), several factors implicated in determination of whether a disclosure satisfies the enablement requirement and whether any necessary experimentation is “undue” are identified. These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). No single factor is independently determinative of enablement; rather “[i]t is improper to conclude that a disclosure is not enabling based on an analysis of only one of the above factors while ignoring one or more of the others.” MPEP 2164.01. Likewise, all factors may not be relevant to the enablement analysis of any individual claim.
“According to In re Bowen, 492 F.2d 859, 862-63, 181 USPQ 48, 51 (CCPA 1974), the minimal requirement is for the examiner to give reasons explaining the uncertainty of the enablement. This standard is applicable even when there is no evidence in the record of operability without undue experimentation beyond the disclosed embodiments.” See also In re Brana, 51 F.3d 1560, 1566, 34 USPQ2d 1436, 1441 (Fed. Cir. 1995); MPEP 2164.04.
The rejected claims all require a deposited strain deposited as KACC 83048BP.
“Biological material need not be deposited unless access to such material is necessary for the satisfaction of the statutory requirements for patentability under 35 U.S.C. 112. If a deposit is necessary, it shall be acceptable if made in accordance with these regulations.” 37 CF 1.802(b). Here, it is not possible to practice the invention of the rejected claims without the specific deposited strain. The specification does not directly state that the strain deposited as KACC 83048BP is specifically one made in the working examples of the specification.
More specifically, for Wands factors (A)-(C), a very specific strain is required to practice the invention such that the only way to obtain the strain, which are not apparent in the working examples. The end of the specification, page 55, states, information about the deposited strain but does not have any explained relationship to the prior working examples. Further, even if the working examples are repeated, strains with slight changes in structure may be obtained. For Wands factors (D)-(H), t is not predictable to obtain the identical deposited strain wherein the details of the deposited strain are not set forth in the specification.
As such, the Wands factors listed above are not deemed to be satisfied in favor of enablement of a deposited strain deposited as KACC 83048BP should have been deposited as set forth in 37 CFR 1.801-1.809 for the satisfaction of the statutory requirements for patentability under 35 U.S.C. 112; however, there is no indication on the present record that such a deposit has been made.
If the deposit was made under the terms of the Budapest Treaty, then an affidavit or declaration by applicants, or a statement by an attorney of record over his or her signature and registration number, stating that the specific strain has been deposited under the Budapest Treaty and that the strain will be available to the public under the conditions specified in 37 CFR 1.808, would satisfy the deposit requirement made herein.
If the deposit has not been made under the Budapest treaty, then in order to certify that the deposit meets the criteria set forth in 37 CFR 1.801-1.809, applicants may provide assurance or compliance by an affidavit or declaration, or by a statement by an attorney of record over his or her signature and registration number, showing that: 1. during the pendency of this application, access to the invention will be afforded to the Commissioner upon request; 2. upon granting of the patent the strain will be available to the public under the conditions specified in 37 CFR 1.808; 3. the deposit will be maintained in a public repository for a period of 30 years or 5 years after the last request or for the effective life of the patent, whichever is longer; and 4. the deposit will be replaced if it should ever become inviable.
37 CFR 1.809 has this further requirement that appears to not be satisfied:
(d) For each deposit made pursuant to these regulations, the specification shall contain:
(1) The accession number for the deposit;
(2) The date of the deposit;
(3) A description of the deposited biological material sufficient to specifically identify it and to permit examination; and
(4) The name and address of the depository.
Claim 7 is 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.
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.
Claim 7 recites a method of producing a genus of any generic “lichen-derived metabolite” by culturing a microorganism as recited in claim 6. Since claim 7 must be broader in scope than claim 8, claim 7 is understood as being directed towards metabolites other than 4-O-demethylbaratic acid, proatranorin I, II or III, atranorin or baeomycesic acid. For example other lichen-derived metabolites are known; for example, Yim et al. (U.S. 2014/0094514 A1), in the claims, describes other metabolites not recited in claim 8 produced by Stereocaulon alpinum.
The specification only describes production of the specific metabolites recited in claim 8 using an organism expressing SEQ ID NO: 1, 3 and/or 5 wherein it is understood that any host recombinant organism will have to other be appropriate for producing such metabolites, such as Ascochyta rabiei (a type of fungus). For example, it is not predictable to produce the lichen-derived metabolites described by Yim by culturing a recombinant microorganism according to claim 6 having only one or more of SEQ ID NOS: 1, 3 and 5 as heterologous genes. “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.” Here, for these reasons, the recited genus of production of any generic lichen-derived metabolite as recited in claim 7 other than those species specifically enumerated in claim 8 wherein it is understood that such genus includes metabolites with very different structure than those recited in claim 8 and requiring different, undisclosed genes to produce the same, such as the metabolites described by Yim. For this reason, the specification fails to provide a sufficient written description of a method of producing a genus of any generic lichen-derived metabolite as recited in claim 7.
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 1-3 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product or natural phenomenon without significantly more. The claim(s) recite(s) a gene that is a product of nature. This judicial exception is not integrated into a practical application because no additional claim features are recited other than a natural product. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because no additional claim features are recited other than a natural product.
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).
The rejected claims are directed towards a composition of matter. An atranorin biosynthesis gene at least having SEQ ID NO: 1 derived from lichen Stereocaulon alpinum is a naturally-occurring gene as evidenced by GenBank, Accession No. MZ277879, 2021, www.ncbi.nlm.nih.gov, that sets forth a gene identical to recited SEQ ID NO: 1 described as being a naturally-occurring gene from S. alpinum found in (i.e. derived from) S. alpinum.
Here, the claims are directed towards a composition of matter. As discussed, the recited atranorin biosynthesis gene of claim 1 includes is a product of nature wherein the rejected claims read on the natural genome of Stereocaulon alpinum. More specifically, SEQ ID NO: 1 is the whole gene as found in S. alpinum including introns. As such, regarding Step 2A, prong one, there is no markedly different characteristic between the claimed gene product and its naturally-occurring counterpart since they are one and the same.
Regarding, step 2A, prong two, “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, the claims recites no additional claim elements.
Regarding Step 2B for the claims, “Step 2B asks: Does the claim recite additional elements that amount to significantly more than the judicial exception”? MPEP 2106.05(II). Here, the claims recites no additional claim elements.
For these reasons, the rejected claims are directed towards a judicial exception.
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) 1-3 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ravaglia et al. (IN VITRO RADICAL-SCAVENGING ACTIVITY, TOXICITY AGAINST A. salina, AND NMR PROFILES OF EXTRACTS OF LICHENS COLLECTED FROM BRAZIL AND ANTARCTICA, Quim. Nova 37, 2014, 1015-21) as evidenced by GenBank, Accession No. MZ277879, 2021, www.ncbi.nlm.nih.gov.
Ravaglia, abstract, discuss the characterization of extract of six lichen species including Stereocaulon alpinum with identification of the presence of atranorin. See Ravaglia. Table 1.
The specification describes that the gene labeled atr1 having recited SEQ ID NO: 1 is found in a naturally-occurring species of S. alpinum voucher specimen (the Korea National Arboretum accession: KHL0017342). As such, the evidence of record supports that the genome of naturally-occurring S. alpinum that produced atranorin inherently contains the an atranorin biosynthesis gene having SEQ ID NO: 1, wherein claim 1 has no requirement of a gene isolated from its natural environment. As such, a naturally-occurring S. alpinum organism reads of the features of claims 1-3 based upon the evidence of record.
Claim(s) 7 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kim et al. (Linking a Gene Cluster to Atranorin, a Major Cortical Substance of Lichens, through Genetic Dereplication and Heterologous Expression, mBio 12, Jun. 2021, e01111-21) (see IDS).
As discussed above, claim 7 is not considered to have support in of Korean Application No. 10-2021-0073669.
Kim, abstract, states:
The depside and depsidone series compounds of polyketide origin accumulate
in the cortical or medullary layers of lichen thalli. Despite the taxonomic and ecological
significance of lichen chemistry and its pharmaceutical potentials, there has been no
single piece of genetic evidence linking biosynthetic genes to lichen substances. Thus, we
systematically analyzed lichen polyketide synthases (PKSs) for categorization and identification
of the biosynthetic gene cluster (BGC) involved in depside/depsidone production.
Our in-depth analysis of the interspecies PKS diversity in the genus Cladonia and a related
Antarctic lichen, Stereocaulon alpinum, identified 45 BGC families, linking lichen PKSs to 15
previously characterized PKSs in nonlichenized fungi. Among these, we identified highly
syntenic BGCs found exclusively in lichens producing atranorin (a depside). Heterologous
expression of the putative atranorin PKS gene (coined atr1) yielded 4-O-demethylbarbatic
acid, found in many lichens as a precursor compound, indicating an intermolecular crosslinking
activity of Atr1 for depside formation. Subsequent introductions of tailoring
enzymes into the heterologous host yielded atranorin, one of the most common cortical
substances of macrolichens. Phylogenetic analysis of fungal PKS revealed that the Atr1 is
in a novel PKS clade that included two conserved lichen-specific PKS families likely
involved in biosynthesis of depsides and depsidones. Here, we provide a comprehensive
catalog of PKS families of the genus Cladonia and functionally characterize a biosynthetic
gene cluster from lichens, establishing a cornerstone for studying the genetics and chemical
evolution of diverse lichen substances.
“To investigate the roles of individual genes, we first generated a “clean host” that showed no appreciable metabolite production by removing the BGC for biosynthesis of solanapyrones from the wild-type As. rabiei (Fig. 4B). Then, we introduced the atr1 gene cloned from the S. alpinum genomic DNA (gDNA) into the “clean host.” Expression and correct intron splicing of the atr1 were confirmed by reverse transcription-PCR (RT-PCR) analyses. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) and nuclear magnetic resonance (NMR) analyses indicated a known lichen depside, 4-O-demethylbarbatic acid (compound 1), was produced by a strain expressing the atr1 gene.” Kim, page 5.
Genbank MZ277879 evidences that the atr1 gene from S. alpinum described by Kim has recited SEQ ID NO: 1.
Kim, page 11, describes the specific methodology of culturing an A. rabiei microorganism transformed with “atr1 gene cloned from the S. alpinum genomic DNA” to produce 4-O-demethylbarbatic acid and other metabolites as to meet all of the features of claim 7.
Allowable Subject Matter
Claims 4 and 6 allowed.
Claim 8 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
Korean Application No. 10-2022-0059678 and Kim et al. (Linking a Gene Cluster to Atranorin, a Major Cortical Substance of Lichens, through Genetic Dereplication and Heterologous Expression, mBio 12, Jun. 2021, e01111-21) have substantially similar disclosure. In addition to atr1, Korean Application No. 10-2022-0059678 and Kim et al. disclose genes atr2 (SEQ ID NO: 3) and atr3 (SEQ ID NO: 5). While the sequences are not expressly disclosed, the evidence of record (including the cited Genbank entries on accompanying PTO-892) make it clear that there is inherent possession of these sequences and enablement by Korean Application No. 10-2022-0059678 to obtain the same. While Korean Application No. 10-2022-0059678 does not specifically discuss generic expression vectors and microorganism host, the same is considered to have implicit support in Korean Application No. 10-2022-0059678 as derived from the specific examples disclosed therein.
Kim is the closest art of record with no other identified art disclosing identification of SEQ ID NOS: 1, 3 and 5, wherein the earliest that the same sequences appear in Genbank is 07/07/2021. However, as far as claims have support in Korean Application No. 10-2022-0059678, Kim is not prior art under 35 U.S.C. 102(a)(1) due to having a later publication date.
SEQ ID NOS: 3 and 5 can be found in:
GenBank, Accession No. MZ277878, 2021, www.ncbi.nlm.nih.gov.
GenBank, Accession No. MZ277877, 2021, www.ncbi.nlm.nih.gov.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TODD M EPSTEIN whose telephone number is (571)272-5141. The examiner can normally be reached Mon-Fri 9:00a-5:30p.
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/TODD M EPSTEIN/Primary Examiner, Art Unit 1652