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 .
Election/Restrictions
Applicant’s election without traverse of a 1000kb sequence of SEQ ID NO: 27 with at least 95% identity to SEQ ID NO: 27 and SEQ ID NO: 43 for the gene not encoded by the second sequence in the reply filed on 2/3/2026 is acknowledged. The elected species are considered for the following rejections.
Application Status
This action is written in response to applicant’s correspondence received on 1/10/2023. Claims 1-5, 9-17, 22-23, 26, and 29-30 are pending. Claims 6-8, 18-21, 24-25, and 27-29 have been previously cancelled. All pending claims are currently under examination.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO’s electronic filing system (see Section I.1 of the Legal Framework for EFS-Web or Patent Center (https://www.uspto.gov/patents-application- process/filing-online/legal-framework-efs-web), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via EFS-Web or Patent Center as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via EFS-Web or Patent Center as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Figure 1 contains nucleotide sequences that are not identified by sequence identifiers (i.e., SEQ ID NOs) in the drawings or in the brief description of the drawings. Drawings containing nucleotide sequences must be accompanied with their proper SEQ ID numbers, either in the drawings themselves or in the brief description of the drawings in the specification. For instance, the brief description of Figure 1 does not include SEQ ID NOs for the sequences listed in Figure 1. Additionally, SEQ ID numbers of the sequences shown in Figure 1 are not shown in the figure itself.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Drawings
The drawings are objected to because the figures are not properly labeled.
37 CFR 1.84 (u)(1) states “The different views must be numbered in consecutive Arabic numerals, starting with 1, independent of the numbering of the sheets and, if possible, in the order in which they appear on the drawing sheet(s). Partial views intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter. View numbers must be preceded by the abbreviation "FIG." Where only a single view is used in an application to illustrate the claimed invention, it must not be numbered and the abbreviation "FIG." must not appear.”
The drawings are objected to because Figures 5A-5D are improperly labeled. Figures 5A-5D contain partial views on separate sheets. For example, Figure 5A spans two separate sheets and is labeled “Fig. 5A” and “Fig. 5A (continued)” but should be labeled “Fig. 5A” and “Fig. 5B”in consecutive order. The same is true for Figures 5B-5D.
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
Claims 15, 16, are objected to because of the following informalities:
Claim 15 recites “nucleic acid construct of comprising” which should be amended to correct the typo by deleting the word “of.”
Claim 16 recites “an expression cassette of comprising” (see first line of step iii) and also “a vector of comprising” “nucleic acid of comprising (see lines 1-2 of step iv) which should be amended to correct the typo by deleting the word “of.”
Appropriate correction is required.
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.
Claims 1-5, 9-17, 22-23, 26, and 29-30 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 1, claim 1 recites: “selected from the group consisting or comprising of,” (line 3). Recitation of “consisting or comprising” renders the metes and bounds of the claim unclear, as it is unclear if the term “consisting” is meant to limit the claim with respect to which compounds may act as inducers. For instance, it is unclear from this claim language if additional inducers are encompassed by the claim, as the claim recites that the inducers “comprise” but also “consist” of a list of inducing agents. For instance, if it meant that the claim broadly encompasses any inducing agent then it is unclear how the term “consisting” in fact limits the claim, or if it does limit the claim.
Similarly, the sequences recited in claim 1 are recited to “comprise of consist” of a portion of a sequence (e.g., see the first lines of items (a) and (b) in claim 1). With regard to the recitation of “comprises or consist” in the claim, in a general, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 1 recites the broad recitation “comprises”, and the claim also recites “consists” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Additionally, claim 1 recites the phrase “comprises a portion of a sequence selected from a group comprising a sequence with at least 80%, 85%,…99%.” (e.g., lines 25-26, and other lines). It is unclear what the composition of such a “portion” is meant to be as presently recited. For instance, it is unclear if the “portion” of the sequence is meant to have for instance 80% identity, or if the “portion” can be selected from a sequence having 80% identity (i.e., the “portion” is one portion of a sequence with 80% but is not required to comprise 80% identity itself).
Claims 2-5, 9-17, 22-23, 26, and 29-30 ultimately depend from claim 1 and do not resolve these 112(b) issues and are therefore also rejected.
Regarding claim 2, claim 2 recites the subjective term “low.” Recitation of the term “low” is subjective, as such a value of “low” is left to the individual interpretation of a practitioner, as no value of comparison in defined in the specification or claims to establish a relative comparison. In other words, it is unclear what the term “low” is being compared with, and furthermore what specifically would constitute “low.”
Regarding claim 4, claim 4 lists examples of lengths which the portion of the sequence could comprise (“for example between 50 and 1500 bp”). The phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 5, claim 5 recites “comprises or consists” of. Claim 5 is therefore rejected for reciting broader and narrower limitations within the same claim (see the rejection of claim 1 for explanation). The phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 9, claim 9 recites “comprises or consists” of. Claim 9 is therefore rejected for reciting broader and narrower limitations within the same claim (see the rejection of claim 1 for explanation).
Claim 10 recites “comprises or consists” of. Claim 10 is therefore rejected for reciting broader and narrower limitations within the same claim (see the rejection of claim 1 for explanation).
Claim 12 recites “comprises or consists” of. Claim 12 is therefore rejected for reciting broader and narrower limitations within the same claim (see the rejection of claim 1 for explanation).
Claim 13 recites “comprises or consists” of. Claim 13 is therefore rejected for reciting broader and narrower limitations within the same claim (see the rejection of claim 1 for explanation).
Claim 14 recites “comprises or consists” of. Claim 14 is therefore rejected for reciting broader and narrower limitations within the same claim (see the rejection of claim 1 for explanation).
Claim 15 recites “comprises or consists” of. Claim 15 is therefore rejected for reciting broader and narrower limitations within the same claim (see the rejection of claim 1 for explanation).
Claim 16 recites “comprises or consists” of. Claim 16 is therefore rejected for reciting broader and narrower limitations within the same claim (see the rejection of claim 1 for explanation).
Claim 17 recites “comprises or consists” of. Claim 17 is therefore rejected for reciting broader and narrower limitations within the same claim (see the rejection of claim 1 for explanation).
Regarding claim 22, claim 22 recites in step b:
PNG
media_image1.png
235
854
media_image1.png
Greyscale
This step is generally unclear. Firstly, the phrase “the native promoter” lacks proper antecedent basis because no native promoter is recited previously in the claims. Furthermore, it is unclear what the phrase “wherein following integration the isolated nucleic acid…is capable of driving transcription of the second sequence the isolated nucleic acid…is integrated into the genome of said cell at a different locus to the locus of the native promoter,” as it is unclear if the isolated nucleic acid is meant to be integrated at two separate loci in succession or if only one integration is occurring and step b is meant to clarify the location of integration.
Furthermore, recitation of “i.e.,” and the phrases which follow “i.e.,” in claim 22 are at the very least inherently redundant, as such phrase is taken to mean “in other words,” where the phrase following “i.e.” is typically understood to be a summary or restatement of what came before the phrase “i.e,” in order to clarify language. It is unclear how or if the phrase “i.e.,” and the phrases after this phrase (repeated throughout the claim) are meant to limit the claim. It is unclear whether the modified terms are an improper recitation of a preference in the claim or an actual claim limitation.
Regarding claim 23, claim 23 recites “comprises the use of the isolated nucleic acid of claim 1.” Claim 23 is therefore a “use” claim, where it is unclear how the nucleic acid is being used. The metes and bounds of the claim are therefore undefined rendering claim 23 unclear.
Claim 26 recites “comprises or consists” of. Claim 26 is therefore rejected for reciting broader and narrower limitations within the same claim (see the rejection of claim 1 for explanation).
Claim 26 furthermore recites that the kit comprises at least two of the recited components a-d. Component “a” is the “isolated nucleic acid of claim 1.” Component “b” for instance is “a nucleic acid construct” comprising a first and second sequence, where the first sequence is the isolated nucleic acid of claim 1. It is unclear if a kit comprising components “a” and “b” (or “c” and “d”) would require both a separate “isolated nucleic acid of claim 1” to satisfy component “a” but also a construct further comprising an additional copy of the “isolated nucleic acid of claim 1.” The contents of the recited kit are in general unclear, as each component b-d also recite the component of “a;” thus, the total number and configuration of “isolated nucleic acid of claim 1” is unclear from the present claim language.
Claim 29 recites “a method of producing a vaccine comprising using the isolated nucleic acid of clam 1.” Claim 29 is a “use” claim, where it is unclear how the nucleic acid is being used. The metes and bounds of the claim are therefore undefined rendering claim 29 unclear. Furthermore, claim 29 recites “optionally, inducible promoter, nucleic acid construct…or a cell.” However, these components are simply listed after the phrase “a method of producing a vaccine comprising using the isolated nucleic acid of claim 1,” which renders the addition unclear as it is unclear what this list of limitations has to do with the method, and/or if they are being used in the method as they are not recited in connection with a use in the method.
No claim which depend from any of the claims recited above clarify the claim language to remedy the 112(b) issues and are therefore also rejected.
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 1-5, 9-17, 22-23, 26, and 30 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more.
Regarding claim 1, claim 1 is drawn to an isolated nucleic acid molecule comprising, for instance, 1000kb of SEQ ID NO: 27 (per applicant’s election). SEQ ID NO: 27 is a 100% match of SEQ ID NO: 4 from Meijrink (US patent 10,590,436 B2, see first two pages for alignment). Meijrink teaches that SEQ ID NO: 4 is the genome of Y. lipolytica (second column, final paragraph, “Description of the Sequence Listing). Thus, instant SEQ ID NO: 27 is simply a nucleic acid sequence in the naturally occurring Y. lipolytica (per SEQ ID NO: 4 of Meijrink). Claim 1 is therefore claiming a naturally occurring product of nature (Step 2A, prong 1 of the Subject Matter Patent Eligibility Test, MPEP 2106). Regarding recitation of the phrase “isolated nucleic acid,” MPEP 2106.04(c), subsection IIC provides guidance with analysis regarding isolated nucleic acid which are naturally occurring sequences:
“In Myriad, the Supreme Court made clear that not all changes in characteristics will rise to the level of a marked difference, e.g., the incidental changes resulting from isolation of a gene sequence are not enough to make the isolated gene markedly different. Myriad, 569 U.S. at 580, 106 USPQ2d at 1974-75. The patentee in Myriad had discovered the location of the BRCA1 and BRCA2 genes in the human genome, and isolated them, i.e., separated those specific genes from the rest of the chromosome on which they exist in nature. As a result of their isolation, the isolated genes had a different structural characteristic than the natural genes, i.e., the natural genes had covalent bonds on their ends that connected them to the rest of the chromosome, but the isolated genes lacked these bonds. However, the claimed genes were otherwise structurally identical to the natural genes, e.g., they had the same genetic structure and nucleotide sequence as the BRCA genes in nature. The Supreme Court concluded that these isolated but otherwise unchanged genes were not eligible, because they were not different enough from what exists in nature to avoid improperly tying up the future use and study of the naturally occurring BRCA genes. See, e.g., Myriad, 569 U.S. at 585, 106 USPQ2d at 1977 ("Myriad's patents would, if valid, give it the exclusive right to isolate an individual’s BRCA1 and BRCA2 genes … But isolation is necessary to conduct genetic testing") and 569 U.S. at 593, 106 USPQ2d at 1980 (describing how would-be infringers could not avoid the scope of Myriad’s claims). In sum, the claimed genes were different, but not markedly different, from their naturally occurring counterparts (the BRCA genes), and thus were product of nature exceptions,” MPEP 2106.04(C), IIC.
Thus, recitation of the limitation that the naturally occurring gene is an “isolated nucleic acid” is not sufficient to render markedly different characteristics upon the recited SEQ ID NO: 27, as such isolation is recognized in the MPEP as not possessing markedly different characteristics compared with a naturally occurring part of an organism’s genome (in the present case, Y. lipolytica, per Meijrink, above). Thus, the recited product does not possess markedly different characteristics (Step 2A, prong 1 of the Subject Matter Patentability Test, MPEP 2106) nor does the claim recite additional elements which would integrate the product into a practical application (Step 2A, prong 2). Regarding other characteristics in the claim (e.g., inducibility by inducing agents), such characteristics are inherent properties of the sequence, and do not provide structural significance to the claimed nucleic acid. The claim does not recite additional limitations which transform the subject matter into significantly more than the judicial exception (Step 2B). Thus, claim 1 is directed to subject matter which is not patent eligible.
Regarding claims 2-3, these claims simply recite inherent characteristics of the recited isolated nucleic acid/promoter. These inherent properties do not add or change the structural limitations of the recited sequence. Therefore, claims 2-3 recite the judicial exception of claim 1 (Step 2A, prong 1) and do not recite any additional elements which would integrate the natural product into a practical application (Step 2A, prong 2) or transform the subject matter into significantly more (Step 2B). Claims 2-3 are therefore not subject matter eligible.
Regarding claims 4-5, these claims are broadly drawn to portions of the recited sequences. As discussed above, “portions” of naturally occurring nucleic acid sequences do not comprise markedly different characteristics when compared with their natural occurrence in the genome (MPEP 2106, Step 2A, prong 1) Thus, the limitations recited in claims 4-5 do not render markedly different characteristics unto, for instance, SEQ ID NO: 27 (Step 2A, prong 1). Furthermore, no additional claim limitations are recited to integrate the claimed subject matter into a practical application (Step 2A, prong 2) or to transform the claim into significantly more than the judicial exception (Step 2B). Claims 4-5 are therefore not patent subject matter eligible.
Regarding claim 9, claim 9 recites “a nucleic acid construct” which comprises the sequence of claim 1. Claim 9 can be most broadly interpreted to be drawn to the chromosome of Y. lipolytica which comprises SEQ ID NO: 4 of Meijrink (i.e., instant SEQ ID NO: 27), where SEQ ID NO: 4 can be considered the “first” nucleic acid sequence while any other sequence on the chromosome can be considered the “second” nucleic acid sequence. Thus, claim 9 is drawn to a naturally occurring product of nature without markedly different characteristics (Step 2A, prong 1). Claim 9 does not recite additional elements which integrate the product of nature into a practical application (Step 2A, prong 2) or transform the claim into significantly more than the judicial exception (Step 2B). Claim 9 is therefore not subject matter eligible.
Regarding claims 10-12, claims 10-12 are drawn most broadly to merely the presence of the nucleic acid of claim 1 in a nucleic acid comprising another sequence capable of being transcribed into mRNA (i.e., a gene). As Meijrink teaches that SEQ ID NO: 27 is a part of the naturally occurring genome of Y. lipolytica, SEQ ID NO: 27 (i.e., the first sequence) is naturally in a nucleic acid construct with a second sequence capable of being transcribed into mRNA (i.e., any gene transcribed from the same chromosome in the genome of Y. lipolytica reads on claims 10-12). As evidenced by Crill (Crill JE et al. J Ind Microbiol Biotechnol. 2026 Jan 8;53), every chromosome of Y. lipolytica encodes genes, and therefore include “second” sequences which can be expressed as mRNA (Table 1 of Crill). With regards to the phrase “operably linked” this phrase is not specifically defined in the specification, and can broadly be interpreted to mean simply any linkage between nucleic acids on a chromosome, as such organization and linkages are operably linked to form the architecture of the chromosome. Thus, claims 10-12 are most broadly drawn to a naturally occurring yeast chromosome of Y. lipolytica without markedly different characteristics, where the first nucleic acid is the naturally occurring SEQ ID NO: 4 (per Meijrink) and the second nucleic acid is simply a gene that is transcribed into mRNA on the same chromosome (Step 2A, prong 1). Furthermore, the claims do not recite additional elements which would integrate the limitations into a practical application (Step 2A, prong 2) or transform the claims into significantly more than a judicial exception (Step 2B). Claims 10-12 are therefore not subject matter eligible.
Regarding claim 13, claim 13 recites that the second nucleic acid does not encode FDH. However, there are no other limitations regarding the second nucleic acid sequence. As such, the “second nucleic acid” sequence can be any other gene on the same chromosome of SEQ ID NO: 4 of Meijrink in the yeast Y. lipolytica. As evidenced by Crill, every chromosome of Y. lipolytica encodes numerous genes, any one of which can be considered a second nucleic acid sequence (Table 1 of Crill). Thus, claim 13 recites a naturally occurring product of nature without markedly different characteristics (Step 2A, prong 1), where furthermore no additional limitations are recited to integrate the judicial exception into a practical application (Step 2A, prong 2) or transform the claim into significantly more than the judicial exception (Step 2B). Claim 13 is therefore not patent eligible.
Regarding claims 14-15, claims 14-15 are broadly drawn to a nucleic acid construct comprising the sequence of claim 1 and a second sequence. Claims 14-15 are therefore broadly drawn to the same subject matter of claim 9 and are rejected using the same rationale applied to claim 9.
Regarding claims 16-17, and 22, these claims are broadly drawn to a yeast cell comprising the sequence of claim 1. As Meijrink teaches, SEQ ID NO: 27 (SEQ ID NO: 4 of Meijrink) is a naturally occurring component of the genome of the yeast cell Y. lipolytica. The cells recited in claims 16-17 and 22 therefore do not recite markedly different characteristics compared with the naturally occurring Y. lipolytica cell (Step 2A, prong 1). Regarding recitation of the term “integrated” in claim 22, such integration can simply be interpreted to mean the natural placement of the sequence within the yeast cell, where furthermore its natural properties as a promoter related to gene expression are also natural, inherent properties of the sequence of the nucleic acid. Furthermore, claims 16-17 and 22 do not recite additional elements to integrate the judicial exception into a practical application (Step 2A, prong 2) or to transform the claim into significantly more than a judicial exception (Step 2B). Claims 16-17 and 22 are therefore not subject matter eligible.
Regarding claim 23, as discussed above in the 112(b) rejection, claim 23 is a “use” claim which does not clearly define a role of the nucleic acid in claim 1 in the production of an expression product or gene. Claim 23 is therefore broadly drawn to a method of producing a gene. MPEP 2106.04(C) section I, subsection C, states that:
“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)
Thus, because claim 23 in its broadest sense is a method claim for a producing a gene, the method claim is broadly drawn to simply a method of producing a natural product. As such, per MPEP 2106.04(C), section I, subsection C, the claim is treated as a product claim drawn to what is being recited to be produced (i.e., a gene). Thus, claim 23 is broadly drawn simply to a naturally occurring gene (Step 2A, prong 1), where furthermore no additional limitations are recited to integrate the judicial exception into a practical application (Step 2A, prong 2) or transform the claim into significantly more (Step 2B). Claim 23 is therefore not patent eligible.
Regarding claim 26, claim 26 is broadly drawn to a cell comprising the nucleic acid construct comprising a first nucleic acid of claim 1 and a second nucleic acid. As such, claim 26 is drawn broadly to the limitations of claims 16-17, and is rejected for the same reasons.
Regarding claim 30, claim 30 is broadly drawn to the cell according to claim 16, and is therefore rejected for the same reasons. Regarding the limitation “food product” which comprises the cell, these limitations do not confer structural significance onto the cell, as such a cell could be reasonably cannibalized and metabolized by another organism (i.e., the cell itself can be considered a food product).
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.
Claims 1-5, 9-17, 22-23, 26, and 29-30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Meijrink (US patent 10,590,436 B2, first published 7/14/2016, issued 3/17/2020). The rejection is further evidenced by the post-filing publication Crill (Crill JE et al. J Ind Microbiol Biotechnol. 2026 Jan 8;53).
Regarding claim 1, Applicant has elected a 1000kb portion of SEQ ID NO: 27. Meijrink teaches SEQ ID NO: 4, which comprises at least such a portion of SEQ ID NO: 27 because SEQ ID NO: 4 matches 100% with instant SEQ ID NO: 27 (see first two pages of Meijrink for alignment of instant SEQ ID NO: 27 and SEQ ID NO: 4). Claim 1 is drawn broadly to a nucleic acid encoding such a sequence. Thus, because Meijrink teaches a 100% match of SEQ ID NO: 27, Meijrink’s SEQ ID NO: 4 anticipates instant claim 1 and Applicant’s elected species.
Regarding claims 2-3, claims 2-3 simply recite inherent properties of the nucleic acid of claim 1. Thus, because Meijrink’s SEQ ID NO: 4 teaches the same nucleic acid sequence (see pages 1-2 of Meijrink), the properties are inherent to the sequence taught by Meijrink. Meijrink’s SEQ ID NO: 4 therefore anticipates the claim limitations of claims 2-3 inherently.
Regarding claims 4-5, claims 4-5 simply recite portions of a sequence such as SEQ ID NO: 27 (applicant’s elected sequence). By teaching SEQ ID NO: 4 which is a 100% match to instant SEQ ID NO: 27, Meijrink inherently teaches portions of the sequence (see alignment on pages 1-2 of Meijrink).
Regarding claim 9, claim 9 is broadly drawn to a nucleic acid comprising a first and second sequence, where the first sequence is the sequence of claim 1. As discussed in the rejection of claim 1, Meijrink teaches such a nucleic acid, as SEQ ID NO: 4 of Meijrink teaches the genome of Y. lipolytica. Furthermore, Crill teaches that every chromosome of Y. lipolytica includes numerous genes; the genome of Y. lipolytica, as well as the chromosome encoding instant SEQ ID NO: 27, is therefore most broadly drawn to the chromosome encoding SEQ ID NO: 27 in Y. lipolytica, as such a chromosome would further comprise a “second sequence” in the form of any of the other genes encoded on the chromosome. Note that, while Crill is a post-filing publication, it is being used simply to show an inherent property which was also present at the time of filing. The use of Crill as an evidentiary reference is therefore acceptable.
Regarding claims 10-12, as discussed above in the rejection of claim 9, Crill teaches that numerous genes, which can reasonably be expressed as mRNA, are present on every chromosome of Y. lipolytica. Thus, SEQ ID NO: 27, which is a component of the genome of Y. lipolytica per Meijrink (SEQ ID NO: 4 of Meijrink, see final paragraph of column 2 of Meijrink) is also taught inherently by Meijrink to be in a nucleic acid with a “second sequence” can be expressed or transcribed as mRNA. With regards to the phrase “operably linked” this phrase is not specifically defined in the specification, and can broadly be interpreted to mean simply any linkage between nucleic acids on a chromosome, as such organization and linkages are operably linked to form the architecture of the chromosome. Claims 10-12 are therefore broadly drawn to the chromosome of Y. lipolytica which comprises instant SEQ ID NO: 27, where such a sequence is taught in the genome taught by Meijrink (SEQ ID NO: 4).
Regarding claim 13, as Meijrink teaches the genome of Y. lipolytica (SEQ ID NO: 4, see above), which comprises instant SEQ ID NO: 27, the “second sequence” can be any such sequence on a chromosome that is also on the chromosome of Y. lipolytica comprising SEQ ID NO: 27. As such, the “second sequence” can be interpreted to be any of the thousands of genes encoded on the chromosome, per Crill (Table 1 of Crill). Therefore, the “second sequence” can be considered to be any gene on the same chromosome as instant SEQ ID NO: 27, where any such gene may be “not” FDH or SEQ ID NO: 43 (applicant’s elected gene).
Regarding claims 14-15, claims 14-15 are broadly drawn to a “nucleic acid construct comprising at least a first and second nucleic acid sequence, wherein the first nucleic acid sequence comprises or consists of the isolated nucleic acid sequence of claim 1.” As such, these claim limitations are identical in scope to claim 9. Claims 14-15 are therefore rejected for the same reasons outlined in the rejection of claim 9.
Regarding claims 16-17, and 22, Meijrink teaches that SEQ ID NO: 4 is part of the genome of Y. lipolytica, and therefore teaches that the nucleic acid comprised in a cell. Furthermore, regarding claim 22, recitation of “following integration” can broadly be interpreted to be the same structure of the genome which exists naturally in the Y. lipolytica genome taught by Meijrink (SEQ ID NO: 4 of Meijrink, column 2, final paragraph of Meijrink), where such a sequence – without evidence to the contrary – can reasonably be interpreted to be a promoter of a gene. Thus, the structure recited in claim 22 appears to read on the naturally occurring genome of Y. lipolytica.
Regarding claim 23, claim 23 is simply drawn to a method of expressing a gene, where for instance SEQ ID NO: 27 is present. Meijrink teaches that SEQ ID NO: 27 (SEQ ID NO: 4 of Meijrink) is present in the genome of Y. lipolytica, where it is further evidenced by Crill that Y. lipolytica produces expression products of genes (Table 1 of Crill). Thus, by teaching the Y. lipolytica genome, where such a cell as Y. lipolytica is known to produce gene products by genetic expression (per Table 1 of Crill), Meijrink is inherently teaching a method by which to produce gene products by teaching a cell which is naturally making such products, if by no other means by simply providing such a cell as Y. lipolytica.
Regarding claim 26, Meijrink teaches that Y. lypolitica comprises SEQ ID NO: 27 (SEQ ID NO: 4 of Meijrink, column 2, final paragraph of Meijrink and pages 1-2 of alignment to SEQ ID NO: 27). Thus, Meijrink teaches both the nucleic acid sequence of SEQ ID NO: 27 and also a cell comprising such a sequence (i.e., a Y. lipolytica cell).
Regarding claim 29, the only actionable step of claim 29 appears to be providing a nucleic acid sequence such as SEQ ID NO: 27. Note that the preamble “a method of producing a vaccine” does not add structural limitations or guidance in the claim itself. As such, as claim 29 is generally unclear, it is here being interpreted that such a method can be drawn most broadly to simply providing SEQ ID NO: 27. Meijrink, by simply teaching SEQ ID NO: 4, which is a 100% match to SEQ ID NO: 27, therefore anticipates such a broad interpretation.
Regarding claim 30, claim 30 is most broadly drawn to a cell of claim 16, as such a cell can reasonably be cannibalized or used as an energy source, either by itself or another microorganism (i.e., the cell itself can be interpreted to be a food product, as no specific definition of “food product” is recited in the specification). Thus, claim 30 is rejected for the same reasons as those outlined in the rejection of claim 16.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-5, 9-17, 22-23, 26, and 29-30 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.
MPEP 2163.II.A.3.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states 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. See Regents of the University of California v. Eli Lilly & Co, 119 F.3d at 1568, 43 USPQ2d at 1406.
Regarding claim 1, claim 1 is broadly drawn to a genus of nucleic acids which are recited to be capable of functioning as inducible promoters, where the promoters are inducible by the introduction of formate, formic acid, formaldehyde, methanol, ethanol, propanol, butanol, and glycerol. Furthermore, the recited genus of nucleic acids are recited to “comprise or consist” of a consensus sequence, or a “portion” of a sequence selected from a list of SEQ ID numbers, or to comprise a “portion” of a sequence selected from a group of SEQ ID numbers, where a percentage of 80-100% of the sequence identity is required. This claim language is problematic for several reasons. Firstly, as will be discussed further below, the only inducing agent which was tested appears to be sodium formate. Thus, the applicant has not shown any promoter which is capable of being induced by, for instance, butanol. Furthermore, the applicant is claiming a genus of uncharacterized promoter sequences, where the sequences are recited with functional requirements (i.e., they must function as promoters which can be induced). The genus of promoter which the applicant is claiming encompasses variations of the SEQ ID numbers which were not reduced to practice. The applicant has not characterized “portions” of the sequences, where such “portions” can be interpreted to be any portion of the sequences (for instance, 10 base pairs of SEQ ID NO: 27). The Applicant has not shown functional embodiments of “portions” of the recited sequences commensurate in scope with what is being claimed.
Regarding the guidance provided in the specification, the applicant offers examples 1-3. Example 1 describes identifying putative promoters (16 promoters), where 10 of these putative promoters for FDH genes show an increased expression level after exposure to sodium formate, where qPCR is used to establish expression levels. Note that, given the fact that not all 16 of the putative promoters function in the same manner is evidence of unpredictability concerning such sequences that are identified. Example 2 details an experiment where a 1500 bp region of one of the promoters is cloned into an expression construct linked with a reporter GFP gene, where the reporter appears to display increased expression in the presence of sodium formate. Example 3 tests different growth medias, where two putative promoters are measured (strains comprising S29008 and p15032). Thus, in total, two promoters have been tested in full length, while a 1500 bp “portion” of one promoter (YALI0E14256, Example 2) was tested.
The Applicant has not identified any core structure-function relationship which would identify common structural features of the promoters and the functional requirement that these sequences act as inducible promoters. For instance, the Applicant has not characterized elements of the promoters through mutagenesis or identified transcription factor binding sites which confer any characteristics on the promoters. The Applicants have therefore not shown possession of what “portions” of the recited sequences are functional, and/or which portions can be mutated or deleted in order to retain the recited functionality of the promoters. Furthermore, the Applicant has only identified 10 putative promoters with such functionality, and was therefore not in possession of any promoters with, for instance, “80%” sequence identity to SEQ ID NO:6. Thus, the Applicant was not in possession of either promoters comprising 80% sequence similarity to the recited sequences and much less “portions” of these sequences, which could comprise as few as 10 base pairs. For instance, the applicant has not established or shown possession of what a minimum “portion” of any of the promoters would be, where such a “portion” must still retain the functionality of a protein, let alone if it would be possible to have a portion as small as, for instance, 10 bp, which could function as an inducible promoter.
Regarding the state-of-the art, it is known in the art that promoters are relatively uncharacterized, where such sequences comprise binding sites for transcription factors, where such binding sites are not fully characterized. For instance, Zhu (Zhu C et al. Genome Res. 2009 Apr;19(4):556-66) teaches that:
“Transcription factors (TFs) regulate the expression of genes through sequence-specific interactions with DNA-binding sites. However, despite recent progress in identifying in vivo TF binding sites by microarray readout of chromatin immunoprecipitation (ChIP-chip), nearly half of all known yeast TFs are of unknown DNA-binding specificities, and many additional predicted TFs remain uncharacterized. To address these gaps in our knowledge of yeast TFs and their cis regulatory sequences, we have determined high-resolution binding profiles for 89 known and predicted yeast TFs, over more than 2.3 million gapped and ungapped 8-bp sequences (‘‘k-mers’’). We report 50 new or significantly different direct DNA-binding site motifs for yeast DNA-binding proteins and motifs for eight proteins for which only a consensus sequence was previously known; in total, this corresponds to over a 50% increase in the number of yeast DNA-binding proteins with experimentally determined DNA-binding specificities,” (Abstract)
Zhu further teaches that such transcription factors bind to promoters (e.g., page 564, right column, final paragraph). Thus, Zhu teaches that transcription factor binding in yeast cells and their promoters is complex and unpredictable, where such transcription factor binding sites are largely unknown and must be characterized by empirical data and experimentation. The application has not shown any such characterization, where it is unknown and unpredictable what sequences of the recited SEQ ID numbers are conferring the functionality of being inducible promoters.
Similarly, Tang (Tang H et al. Metabolites. 2020 Aug 6;10(8):320) is a research article which focuses on promoter engineering in yeast cells (Title, Abstract, and throughout). Tang teaches that there is inherent unpredictability and complexity within endogenous promoters, teaching that:
“Alper created a library based on the TEF1 promoter and obtained a series of synthetic promoters with a wide range of activities; the best candidate showed a two-fold higher activity than the native PTEF1. These promoters were used to regulate efficient glycerol production by driving the rate-limiting enzyme expression in S. cerevisiae,” (page 8, thir paragraph).
Thus, Tang teaches that random mutagenesis libraries create promoters with a “wide range” of activity. Furthermore, as seen above, Tang teaches that such activities must be validated empirically.
Thus, given that promoters and their architecture, along with the binding sites which they comprise for transcription factors, are widely uncharacterized and unpredictable, and where furthermore such components are known to affect the functionality of the promoters, the applicant can not be said to have been in possession of the genus of promoters presently recited, as they have not performed any mutagenesis studies to identify structural elements of the promoters required for functionality or identified any transcription factor binding sites or essential functional regions of the promoters, and have at best only generated one “portion” of one of the promoters which comprised at least 1500 bp of one of the putative promoters.
Furthermore, as discussed above, the applicant has only tested one inducing agent (sodium formate). The applicant has not tested, for instance, butanol, let alone have they tested butanol within the large genus of nucleic acids and “portions” of said nucleic acids presently recited, to show sufficient possession of “portions” of nucleic acids/promoters which are inducible by any other agents besides sodium formate.
Furthermore, given that the promoters themselves which were inducible showed a range of induciblity from 2.9-38.6 depending on the promoter (Table 1 of the specification), the data appears to show wide range of variability across the promoters identified. There is therefore no indication that testing one “portion” of 1500 bp of one of the promotes would reasonably show possession of the remaining, untested promoters, as the identified promoters appear to show highly variable results (table 1 of specification).
Claims 2-5, 9-17, 22-23, 26, and 29-30 depend from claim 1 and do not resolve this 112(a) issue and are therefore also rejected under 112(a).
Furthermore, regarding claim 3, claim 3 recites fold-changes as high as 50-fold when cultured in YNB with 0.5% formate. However, the maximum fold-change presented in Table 1 of the specification is 38.6 (see Table 1 of the specification). Thus, the Applicant has not shown an inducible promoter with over 38.6-fold induction, and was therefore not in possession of such claim limitations as those recited in claim 3.
Furthermore, regarding claims 4-5, these claims recite sequence portions as small as 46 base pairs. However, as discussed above, the smallest portion tested was one portion of one promoter, which was 1500 bp (Example 2 of the specification). As discussed above, the applicant has not shown possession of regions that are as short as 46 base pairs, as it is known that promoters comprise transcription binding sites and also unpredictability with regards to what domains of a promoter can be mutated in order to retain functionality (see rejection of claim 1). Thus, as discussed in the rejection of claim 1 and reiterated here, the applicant was not in possession of nucleic acids which were less than 1500 bp, and as small as 46 base pairs, as they have not characterized such portions of the sequence which would function as inducible promoters.
Furthermore, regarding claim 29, claim 29 recites a method of producing a vaccine using the nucleic acid of claim 1. However, the Applicant has not demonstrated or recited any such method to produce a vaccine in the specification or drawings. The Applicant has therefore not shown possession of any method of vaccine production using the nucleic acid of claim 1, let alone the unpredictable genera recited in claim 1, which further adds unpredictability and complexity to a method of vaccine production.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DOUGLAS CHARLES RYAN whose telephone number is (571)272-8406. The examiner can normally be reached M-F 8AM - 5PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ram Shukla can be reached at (571)-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/D.C.R./Examiner, Art Unit 1635
/KIMBERLY CHONG/Primary Examiner, Art Unit 1636