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 of Group I (claims 1-8, 10, 12, 13, 15 and 18-21) in the reply filed on July 22, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 22-25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-8, 10, 12, 13, 15 and 18-21 are examined below.
Priority
The present application is a 35 U.S.C. 371 national stage filing of the International Application No. PCT/EP2022/066763, filed June 20, 2022, which claims foreign priority 35 U.S.C. 119(a)-(d) to GB 2108855.4 filed on June 21, 2021.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Thus, the earliest possible priority for the instant application is June 21, 2021.
Information Disclosure Statement
The information disclosure statement filed July 1, 2024; Sept. 11, 2024; Feb. 27, 2025; and July 22, 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDSs have been considered by the examiner.
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 1-8, 10, 12, 13, 15, and 18-21 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. Claim 1 recites, “A method of modifying a complementary DNA (cDNA) sequence for expression in a eukaryotic cell comprising; providing a nucleic acid molecule comprising a cDNA sequence, wherein the cDNA sequence comprises two or more splicing consensus motifs that divide the cDNA sequence into exon regions of 50 to 1200 nucleotides, inserting heterologous introns into the splicing consensus motifs of the cDNA sequence, wherein each heterologous intron comprises a 3' region having a GC content equal to or lower than the GC content of a 5' region of the immediately downstream exon region, thereby producing a nucleic acid molecule comprising a modified cDNA sequence for expression in a eukaryotic cell.” The underlined terms render the claim indefinite. It is not clear how long the 3’ region has to be, where exactly it starts or ends and what exactly it is being compared to. Likewise, it is not clear how long the 5’ region of the downstream exon region has to be, where exactly it starts or ends. Are equivalent regions being compared – e.g. a 30 nucleotide 3’ intronic region being compared to a 30 nucleotide 5’ exon region? As the claim is currently written any subset in what is deemed to be the 3’ intronic region (1 nucleotide, 3 nucleotides, 5 nucleotides) could be compared to any subset of what is deemed to be the 5’ exon region (30 nucleotides? 300 nucleotides? 1200 nucleotides?). Any cDNA construct with two or more splicing consensus motifs with a heterologous intron having at least a GC in it and an exon downstream from it with 50 – 1200 nucleotides could potentially be viewed as being included in the claimed subject matter. Additionally, the asserted “method of modifying a complementary DNA (cDNA) sequence for expression in a eurkayotic cell” is unclear – is “expression” required? The steps of the claims do not seem to support this, but the preamble appears to indicate that expression is happening. It is suggested that the preamble be modified to recite “a method of increasing the expression of a cDNA sequence in a eukaryotic cell comprising modifying the cDNA through the following steps…”
Claim 13 is further rejected because 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 13 has two issue where this indefiniteness occurs: (1) the broad recitation of the amino acid sequence (C/A/G)AGG(T/N)(T/N), and the claim also recites “optionally…CAGGTT” which is the narrower statement of the range/limitation and (2) “(C/A/G)AGG(T/N)(T/N)” as “N” denotes any nucleotide, where “T” requires a specific nucleotide. The recitation of both causes indefiniteness in that if it can be any nucleotide, why would a specific nucleotide then further be recited? 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.
Conclusion
The claims have been determined to be unsuitable for examination due to issues
with indefiniteness described above. The following prior art made of record is considered pertinent to applicants' disclosure:
Amit et al (Cell Rep, 2012, cited in IDS file don July 1, 2024) teach a study that examines the importance of the relative 3’/5’ GC content in relation to introns, including the modification of GC content of the middle exon of multiple minigenes (pg. 550, Fig. 5, 6) (“In conclusion, we have shown that transforming a minigene without an exon-intron GC content differential into one that has a GC differential rescues splicing of an otherwise skipped exon; in contrast, loss of exon-intron GC content differential inhibited exon recognition. These results indicate that the GC content differential between exons and their flanking introns is a major component in the exon selection process.” (pg. 550, Generating Exon-Intron GC Content Differential Rescues Splicing”) and “Our findings indicate the importance of the exon-intron GC content differential in the correct identification of exons by the splicing machinery”. Applicants own post-priority date publication (Tomberg et al. (BioRxiv, 2021, cited in IDS filed on Feb. 27, 2025) cites the Amit et al. as the research upon which they are building. Applicants claims need to more accurately reflect what they have discovered that is different from what was already known and clearly claim that inventive concept.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TERESA E KNIGHT whose telephone number is (571)272-2840. The examiner can normally be reached Monday-Friday 9-4.
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, Maria Leavitt can be reached at 571-272-1085. 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.
/TERESA E KNIGHT/Primary Examiner, Art Unit 1634
