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 .
Response to Amendment/Status of Claims
Receipt of Arguments/Remarks filed on 08/27/2025 is acknowledged. Claim 1 was amended. Claims 1-20 are pending and are under examination.
Response to Arguments
Applicant's arguments filed 08/27/2025 regarding the Sequences Disclosures have been fully considered but they are not persuasive. Regardless of Applicant’s arguments that Figures 2-4 and 7A have no technical significance in the sequences themselves, nucleotide sequences of 10 or more nucleotides in length 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. See also MPEP 2422.01.
Regarding the Status of Priority claim and applicant’s response on page 8, the examiner is not requiring an English language translation at this time, and was simply noting that the priority application was not in English.
Applicant’s arguments, see page 9, filed 08/27/2025, with respect to the objection to claim 1 have been fully considered and are persuasive. The objection to claim 1 has been withdrawn due to the amendments to claim 1 reciting “a coding region” rather than “a code region”.
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 patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), 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 the USPTO patent electronic filing system 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 the USPTO patent electronic filing system 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. See Figures 2D,3, 4A,4B, 7A, 7B and 8 which show nucleotide sequences over 10 nucleotides in length without sequence identifiers. The Brief Description of the Drawings also does not identify these sequences by sequence identifiers (SEQ ID NOs).
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.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See at least pages 37, paragraph 0067, and page 42, paragraph 0077.
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 1-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1-8 and 11-20 encompass a large genus of translation template mRNAs including a large genus of translation enhancers. The genus of translation enhancers is a combination of a genus of a first sequence that is a nucleic acid as a 5’ untranslated region connected adjacent to a 5’ terminal of the coding region that codes the amino acid sequence of the target protein, and a genus of a second sequence that is a nucleic acid as a 3’ untranslated region connected adjacent to a 3’ terminal of the coding region that codes the amino acid sequence of the target protein, and wherein the sum of the number of nucleic acids on the 3’ side from the conjugation of the first sequence and the number of nucleic acids on the 5’ side from the conjugation of the second sequence is less than or equal to 25. Claim 9 encompasses producing a large genus of translation template mRNA, and claim 10 encompasses producing a large genus of proteins using the large genus of translation template mRNAs of claim 1 produced by claim 9.
While the state of the art teaches cell-free protein synthesis systems using translation enhancers such as those taught in US 20180119154 (‘154), Published 3 May 2018 and cited on an IDS, the state of the art does not teach cell-free protein synthesis systems using translation template mRNA with the recited size limitations regarding the sum of the number of nucleic acids on the 3’ side from the conjugation of the first sequence and the number of nucleic acids on the 5’ side from the conjugation of the second sequence is less than or equal to 25. ‘154 teaches a translation enhancer for cell-free protein synthesis with at most 200 bases in length as a 3’ UTR linked adjacent to the 3’ end of a coding region that encodes the amino acid sequence of a desired protein (Abstract, and paragraph 0016-0017). However ‘154 does not teach a translation enhancer as comprising a sequence as a 5’ UTR or the recited length requirements.
Therefore, due to the lack of teaching in the state of the art regarding the recited size of the translation enhancer, one of ordinary skill in the art would look to the instant specification for guidance on the required structure (sequence) that would perform the function as a translation enhancer and the function of synthesizing a protein.
The specification discloses that the length of nucleic acids of the first sequence 2 is not particularly limited as long as conjugation with the second sequence 3 is formed (paragraph 0020) and there is no upper limit in the length of the first sequence 2 as long as the first sequence 2 can form conjugation with the second sequence 3 and the length is within the range that enables synthesis of a target protein, and the first sequence 2 and the second sequence 3 are designed so as to have the complementary sequence forming conjugation and thereby the first sequence 2 can be shorter than the conventional 5’UTR (paragraph 0021). However, claim 1 limits the sum of the first and second sequence to 25 nucleic acids or less. Table 2 on page 32 lists the sequences for the first sequence of translation enhancer, which are SEQ ID NOs: 4-22, shown below, which varies from 5-33 nucleotides in length.
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420
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Table 1 on page 31 lists the sequence of a T7 promoter, the GFP-His and 3’UTR. Paragraph 0070 discloses that the mechanism by which the 5’UTR can be shortened is not clear and is inferred based on the structures of Figures 7A and 7B that the positions of the start codon and stop codon come closer to each other due to the formation of the conjugation and next translation may be started promptly after the end of previous translation. Example 21 discloses the sequence forming the conjugation C of the second sequence 3 was “GGCCC”.
However, claims 1-20 are directed to encompass a translation enhancer which only corresponds in some undefined way to specifically instantly disclosed translation enhancers. There is no structure-function correlation for the claimed genus of translation template mRNA including a genus of translation enhancers, as to what core structure is required to have the function as a translation enhancer and enhance translation for protein synthesis. The disclosure of SEQ ID NOs: 4-22 in Table 2 is not a representative number of species to meet the written description requirement for the claimed broad genus of translation enhancers. The translation enhancers do not meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, due to lacking chemical structural information for what they are, and chemical structures are highly variant and encompass a myriad of possibilities. The specification provides insufficient written description to support the genus encompassed by the claim. Note: MPEP 2163.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, (Fed. Cir. 1991), makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
Univ. of Rochester v. G.D. Searle, 69 USPQ2d 1886, 1892 (CAFC 2004), further
supports this by stating that:
The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement. A description of an anti-inflammatory steroid, i.e., a steroid (a generic structural term) described even in terms of its functioning of lessening inflammation of tissues fails to distinguish any steroid from others having the same activity or function. A description of what a material does, rather than of what it is, usually does not suffice…. The disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described. (Emphasis added).
With the exception of the above specifically disclosed chemical structures
disclosed in Table 1 and Table 2, the skilled artisan cannot envision the detailed
chemical structure of the encompassed translation template mRNA including a
translation enhancer as recited in instant claims 1-20. Adequate written description
requires the chemical structure itself. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed.
Circ. 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016,
(Fed. Cir. 1991). In Fiddes v. Baird, 30 USPQ2d 1481, 1483, (Bd. Pat. App. & Int.
1993), claims directed to mammalian FGF's were found unpatentable due to lack of
written description for the broad class. The specification provided only the bovine
sequence. Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404,
1405 (Fed. Cir. 1997) held that:
...To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.
Furthermore, to the extent that a functional description can meet the requirement for an adequate written description, it can do so only in accordance with PTO guidelines stating that the requirement can be met by disclosing “sufficiently detailed, relevant identifying characteristics,” including “functional characteristics when coupled with a known or disclosed correlation between function and structure.” Univ. of Rochester v. G.D. Searle, 68 USPQ2d 1424, 1432 (DC WNY 2003).
Therefore, only the above chemically structurally defined translation enhancers, but not the full breadth of the claim(s) meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. The species specifically disclosed are not representative of the genus because the genus is highly variant. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 USC § 112 is severable from its enablement provision. (See page 1115.)
Response to Arguments
Applicant's arguments filed 08/27/2025 have been fully considered but they are not persuasive.
Applicant argues on page 9 of response that the problem to be solved by the instant invention is to shorten the 5’ UTR in a cell-free protein synthesis system without introducing a particular translation enhancement sequence into the 5’ UTR, as described in paragraphs [0010-0012] of the as-filed PCT specification. Applicant states on page 10 that the problem is solved by the technical feature of “wherein the first sequence and the second sequence from a conjugation when the translation template mRNA is analyzed by MXfold, and wherein a sum of the number of nucleic acids on the 3’ side from the conjugation of the first sequence and the number of nucleic acids on the 5’ side from the conjugation of the second sequence is less than or equal to 25” as in claim 1. Applicant argues that even when the same “GGCCC” is used as part of the second sequence, the structure of mRNA changes significantly as shown in Figures 7A, 7B and 8, but that by having the feature as recited in claim 1, the examples solve the problem. Applicant argues on page 11 that this suggests that it is not a specific sequence but the structure recited in claim 1 that is important for solving the problem, and that paragraph 0070 of the specification states, “it is inferred that, in view of the secondary structure of Fig. 7A and Fig. 7B, the positions of the start codon and the stop codon come closer to each other due to the formation of the conjugation C, and next translation may be started promptly after the end of previous translation.
This is not found persuasive. The specification does not provide sufficient written description for the genus of translation enhancers encompassed by the instant claims. While applicant argues it is not a specific sequence that performs the function, and argues the structure in the instant claims solve the problem, this does not meet the written description requirement. 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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The instant claims encompass substantial variation within the genus. Reciting and disclosing that the first and second sequences form a conjugation, and that the sum of the number of nucleic acids on the 3’ side from the conjugation and the number of nucleic acids on the 5’ side from the conjugation of the second sequence is less than or equal to 25, does not provide adequate written description. The disclosure of the sequences of the first sequence and the second sequence described in the written description rejection does not represent the entire genus as claimed, and does not provide a structure-function correlation or core structure necessary for performing the recited function. See MPEP 2163 II. A.3: Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014)
Applicant argues on page 11 that in co-pending Application 17/269,186 a notice of Allowance was issued by specifying the length of the PolyA and the presence of a hairpin structure, without specifying a concrete sequence of the translation enhancer, and therefore, in the present application as the structure that the mRNA can assume is clearly specified, the 112(a) requirements are satisfied.
This is not found persuasive. Patentability decisions made during previous proceedings before the Office concerning the claims of any given patent have no bearing on patentability decisions made with respect to future proceedings concerning different patents having different claims. The Office must decide each case on its own merits, and the similarity of claims found patentable by another Examiner is not material to this proceeding. See In re Wertheim, 541 F.2d 257, 264 (CCPA) (“it is immaterial in ex parte prosecution whether the same or similar claims have been allowed to others”); see also In re Nett Designs, 236 F.3d 1339, 1342 (Fed. Cir. 2001) (“The Board must decide each case on its own merits [and] the PTO’s allowance of prior registrations does not bind the Board or this court”).
In addition, the only instant claims that recite a poly-A sequence are claims 5,7,11-13,17-19 and the poly-A sequence is part of the second sequence. The instant claims do not recite a length of the poly-A. The instant specification discloses a poly-A with a length of 15 on page 30, paragraph 0051, and which is shown in Table 1, SEQ ID NO: 3. In addition, while instant claim 1 recites that the sum of the number of nucleic acids on the 3’ side from the conjugation of the first sequence and the number of nucleic acids on the 5’ side from the conjugation of the second sequence is less than or equal to 25, it does not recite a length or range of lengths for each of the first sequence and the second sequence, as some of the independent claims do. There is no structure-function correlation for the claimed genus of translation template mRNA including a genus of translation enhancers, as to what core structure is required to have the function as a translation enhancer and enhance translation for protein synthesis.
Therefore, the examiner is maintaining the 35 U.S.C. 112(a) Written Description Rejection.
Conclusion
Claims 1-20 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHANIE L SULLIVAN whose telephone number is (703)756-4671. The examiner can normally be reached Monday-Friday, 7:30-3:30 EST.
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 R Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/STEPHANIE L SULLIVAN/Examiner, Art Unit 1635
/ABIGAIL VANHORN/Primary Examiner, Art Unit 1636