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 .
DETAILED ACTION
Claim status
Claims 1-20 are pending
Claims 8, 17-20 are withdrawn
Claims 1-7, and 9-16 are under examination
Election/Restrictions
Applicant’s election of the following invention in the reply filed on 4/28/2026 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 § 818.03(a)).
The requirement is still deemed proper and is therefore made FINAL.
Group I, claims 1-16, drawn to method of estimating the adaptiveness of a transcript.
Claims 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable linking claim.
Applicant’s election of the following species is acknowledged.
Claim 7 directed to strings comprising a coding sequence.
Claim 8 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic claim.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 3/27/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
However, Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claims 14-16 are objected to because of the following informalities: Applicant is advised that should claims 2, 12 and 3 be found allowable, claims 14,15, and 16, respectively, will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 706.03(k).
Claim Rejections - 35 USC § 112(b)
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 13 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 pre-AIA the applicant regards as the invention.
Claim 13 recites the limitation "said host cell" in regard to the gene expression machinery of “a cell”. There is insufficient antecedent basis for this limitation in the claim because Claim 3 is withdrawn, thereby rendering Claim 1 incomplete. Appropriate correction is required.
Claim Rejections - 35 USC § 112(d)
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 and 5 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 draws to a method of estimating the adaptiveness of a transcript comprising generating a reference set of polynucleotide sequences, which does NOT narrow the scope of claim 1 where the generated strings are part of a reference set of polynucleotides. Essentially, due to the Applicant’s own claim language, the step of generating a reference set of claim 2 must already be incorporated into the method of claim 1 in order to establish the generated string is encompassed by the reference set.
Claim 5 draws to a method of estimating the adaptiveness of a transcript based on the length of strings that is calculated in terms of amino acids, which does NOT narrow the scope of claim 1 where the strings are genetic elements. Note that Applicant’s specification defines genetic elements as codon fragments, codon pairs, or nucleotides (p. 5, lines 20-25). Essentially, due to the Applicant’s own claim language, the amino acid embodiment of claim 5 is excluded from the scope of claim 1.
Applicant may cancel the claims, amend the claims to place the claims in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims comply with the statutory requirements.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 4-7, and 9-15 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Raab et al. (US 8,224,578, patented 7/17/2012, see IDS filed 3/27/2023)
Raab teaches a method for designing an optimizing a nucleic acid sequence for expression of a protein of interest in a host cell comprising an iterative codon optimization algorithm (Abstract, col 1, 1st para.).
Raab teaches that adaptation of the codon usage of a synthetic gene to the codon usage of the host organism is one of the most important criteria in the optimization (col 16, lines 38-40). Raab explains that because the frequency with which different organisms use codons for expressing an amino acid differs (called the codon usage), when a synthesized nucleotide transcript is to be used in a particular organisms, the choice of the codons ought to be adapted to the codon usage (CU) of the appropriate organism (col 1, 2nd para.). Note in regard to claim 13, Raab teaches the protein of interest is endogenous to the host cell (col 14, lines 1-30, see Example 3).
In regard to claims 1 and 13, the method comprises the following steps:
First, Raab teaches the step of using a computer unit to generate a set of test sequences (i.e., strings) of “n” codons which correspond to “n” consecutive amino acids in the protein sequence (col 2, lines 43-52, col 12, lines 1-5, see also Fig. 2). Raab teaches each string is a subsequence of the protein’s transcript (see Fig. 2), and comprises subsequence of a reference set of polynucleotides of said host cell in order to assess the adaptiveness of the optimized test sequence. Specifically, Raab determines the quality function for a transcript as the combination of CU score, GC content, and the exclusion of homology regions “to a predefined DNA sequence, for example to the genome of a predefined organism” (col 5, 3rd para. to col 6, 1st para.). Raab teaches CU score is proportional to the sum of the relative adaptiveness of a transcript, which encompasses the frequency of the codon which expresses most frequently for the amino acid in the corresponding organism (col 6, lines 45-59). Therefore, Raab discloses the presence of a prerequisite reference set of polynucleotide sequences from the genome of predefined organism, and the quality of a codon is defined through the frequency of use in the transcriptome or a gene reference set of the host organism (col 8, 1st para.).
Second, Raab teaches using a computer unit to search said sequences to select degenerate substrings of consecutive codons to be optimized (i.e., “CDS”) (col 2-col 3, col 9 to col 10, col 11, last para. to col 12, line 41, col 15, lines 10-55, see Fig. 1 & 2), concatenating (i.e., “connecting” or “joining”) said substrings of codons (col 3, lines 45-55, col 4, last 3 para., see Fig. 1) to form a new test sequence. Raab teaches the parameters can be varied in the test sequence with the aim to “maximize the number of varied codons for the purpose of the best possible optimization” (col 16, 3rd para.). Furthermore, Raab teaches m is the number of amino acids, which corresponds to DNA sequences of 15 to 30 consecutive nucleotides (i.e., “3m bases”, see col 2, lines 53-58, col 15, 2nd para., see also Fig. 1). Considering that Raab teaches the prior art assessed sequences as short as 1 codon of 3 bases, one of ordinary skill in the art would have considered 5 to 10 codons as a selecting a string of codons based on length of the strings.
Finally, as stated supra, Raab teaches providing a statistical measure such as a CU score or RSCU score, that is indicative of the adaptiveness of the transcript sequence (col 6, line 47 to col 7, last para., col 16, 6th para.).
In regard to claims 2 and 14, as stated supra, Raab teaches in order generate a CU score, the frequency of use a codon in the transcriptome or a gene reference set of the host organism must be known. Therefore, Raab implicitly generated a reference set.
In regard to claim 4, as stated supra, Raab teaches the CU score is proportional to the sum “Si” of frequencies of the codon usage (col 6, lines 47-49). Raab also teaches a RSCU score for a codon position, wherein the RSCU is summed for the respective test sequence over all the codons of the test sequence (col 7, 4th para.).
In regard to claims 5, 6, 9 and 10, as stated supra, the length of a string is calculated in terms of codons, or nucleotides, and strings can include pairs of codons and fragments thereof (see also col 23-40).
In regard to claim 7, Raab teaches the method is directed to a genus of proteins of interest to be expressed in a genus of host cells (col 14, lines 1-33, col 13, last para), wherein Raab teaches said strings of codons are capable of encoding a portion of the protein of interest (Figs 1 & 2).
In regard to claims 11 and 12, and 15, as state supra, Raab discloses the presence of a prerequisite reference set of polynucleotide sequences from the genome of predefined organism, and the quality of a codon is defined through the frequency of use in the transcriptome of the host organism, which comprises the entire expressed genome of the host cell.
Accordingly, Raab anticipates instant claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 3 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over (US 8,224,578, patented 7/17/2012, see IDS filed 3/27/2023) in view of Zhang et al. (US2011/0270533, filed 7/13/2011, published 11/03/2011)
Raab teaches a method for estimating the adaptiveness of a transcript sequence encoding a polypeptide of interest comprising generating a string of genetic elements.
Although Raab teaches the parameters can be varied in the test sequences with the aim to “maximize the number of varied codons for the purpose of the best possible optimization”, they indicate that the size of the variation window ranges from 5 to 10 amino acids/15 to 30 consecutive nucleotides. Thus, Raab does not explicitly teach selecting the longest string.
Nevertheless, Zhang teaches an anchor extension mapping methods for aligning contiguous portions of a string of nucleotides to a reference sequence (Abstract, see Fig. 4). Importantly, Zhang teaches the step of increasing the length of the anchor region within the read and perform the string mapping on the new anchor region.
Accordingly, it would have been obvious to one of ordinary skill in the art at the time the invention was filed to practice the method of estimating the adaptiveness of a transcript encoding a polypeptide of interest comprising generating a string of genetic elements as taught by Raab et al. and to increase the length of an anchor region when mapping said strings to a reference sequence so as to select longer strings as taught by Zhang with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Zhang because anchor regions of greater length tend to increase the selectively of the matching [0091].
Hence, the claimed invention was prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Doug Schultz can be reached on 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ARTHUR S LEONARD/Examiner, Art Unit 1631
Prosecution Insights