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 Group I (claims 1-3, 6-12, and 14-16) in the reply filed on June 15, 2026 is acknowledged. Applicants also elected the following species, also without traverse: BspQI (Type IIS restriction endonuclease); E. coli N15 phage TelN (protelomerase); and pUC57-derived vector (cloning vector). It is noted that Applicants list TelN from E. coli N15 phage and SEQ ID NO: 1 as the nucleotide sequence of the vector. However, the claims under examination do not require the specific TelN protelomerase or a pUC57-derived vector having SEQ ID NO: 1.
Claims 17-21, 23-24, 26, and 28-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on June 15, 2026.
Claims 1-3, 6-12, and 14-16 are under examination.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. However, no certified translation of Chinese Patent Application No. CN202110087186.9 has not yet been filed.
Information Disclosure Statement
The Information Disclosure Statements filed July 21, 2023; July 30, 2024; March 19, 2025; May 12, 2025; October 29, 2025; and November 18, 2025 have been considered.
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 specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, 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.
The specification contains sequences that do not include the appropriate sequence identifiers at page 5, lines 5 and 14; page 20, line 14; and page 21, line 3.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code at page 17, line 1; page 20, line 25; page 21, line 18; page 22, line 5; page 26, line 22; page 27, line 6; and page 33, line 10. 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.
The use of the terms TOUCHLIGHT® at page 2, line 23; SINOPHARM® at page 25, lines 9 and 10; and page 30 lines 6 and 7; MILLI-Q® at page 25, line 4; NANODROP® at page 26, line 1 and page 30, line 28; SEPHAROSE® at page 26, line 6 and page 31, line 4; ÄKTA® at page 26, line 7; BIOANALYZER® at page 28, line 8 and page 29, line 11; CYTOFLEX® at page 31, line 4; GENSCRIPT® at page 33, line 7; and THERMOPOL® at Tables 1 and 4; which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 3, 6, 9-10 are objected to because of the following informalities:
At claim 3, line 4, “endonuclease is” should be changed to “endonucleases are.”
At claim 3, line 5, “meganuclease is” should be changed to “meganucleases are.”
At claim 6, line 2, “exonuclease is” should be changed to “exonucleases are.”
At claim 9, line 4, “the IIS type restriction endonuclease and/or meganuclease” should be changed to “the IIS type restriction endonucleases and/or meganucleases”
At claim 10 lines 2-3, “the IIS type restriction endonuclease and/or meganuclease” should be changed to “the IIS type restriction endonucleases and/or meganucleases”
At claim 10 line 4, “exonuclease” should be changed to “the exonucleases”
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 1-3, 6-13, and 14-16 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 the limitation "the transferred DNA construct" in line 3. There is insufficient antecedent basis for this limitation in the claim. It is suggested that “transferred” be deleted.
Claim 1 recites the limitation "the protelomerase" in line 9. There is insufficient antecedent basis for this limitation in the claim. It is suggested that “the” be changed to “a.”
Claims 2-3, 6-12, and 14-16 depend from claim 1 and are therefore included in these rejections.
Claim 2 recites the limitation "the protelomerase" in line 1. There is insufficient antecedent basis for this limitation in the claim.
At claim 2, line 4, the phrase “a variant thereof” is indefinite. While the specification recites that the variant “may include truncation, insertion, substitution, and/or deficiency relative to the natural amino acid sequence of the protelomerase,” it is not clear how similar to the natural amino acid sequence of the protelomerase must the variant be in order to function as required by the claims.
Regarding claim 3, the phrase "for example" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 8 recites “an additional purification step,” which is unclear because there is no first purification step in claim 1, from which claim 8 depends.
At claim 9, lines 2-3, it is not clear what is meant by the phrase “a temperature appropriate for protelomerase activity.” There are no conditions or temperatures set recited in the claims that are considered “appropriate” for protelomerase activity.
At claim 9, lines 3-4, it is not clear what is meant by the phrase “a temperature appropriate for the IIS type restriction endonuclease and/or meganuclease.” There are no conditions or temperatures set recited in the claims that are considered “appropriate” for IIS type restriction endonuclease and/or meganuclease activity.
At claim 9, lines 5-6, it is not clear what is meant by the phrase “a temperature appropriate for the exonuclease.” There are no conditions or temperatures set recited in the claims that are considered “appropriate” exonuclease activity.
Claim 10 recites the limitation "the protelomerase" in line 1. There is insufficient antecedent basis for this limitation in the claim.
L1 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 12 recites the broad recitation “the cloning vector is a plasmid,” and the claim also recites “the cloning vector is derived from: a pBR322 vector, a pUC vector or a pET vector,” 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.
Claim Rejections - 35 USC § 103
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 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, 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 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 1-3, 7-9, 11-12, and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Scharenberg et al. (PCT Patent Application Publication No. WO 2016/057850, published April 14, 2016, and cited in the Information Disclosure Statement filed July 30, 2024) as evidenced by pUC57 (Genescript, 1999).
Regarding claims 1 and 11, Scharenberg discloses method for producing a target DNA sequence comprising the steps of culturing a host cell containing a DNA construct, amplifying and extracting the DNA construct, a first cutting reaction comprising contacting the DNA construct with a protelomerase to form a first cutting reaction mixture, a second cutting reaction comprising contacting the first cutting reaction mixture with a type IIs restriction endonuclease to obtain a second cutting reaction mixture, and digesting the second cutting reaction mixture with an exonuclease to digest sequences other than the target DNA sequence (paragraphs [0007]-[0009], [0067] and [0073]). Scharenberg discloses that the polynucleotide has left and right arms, which is interpreted as the lateral wings of the target DNA sequence (paragraph [0008]).
Regarding claim 2, Scharenberg discloses that the protelomerase can be telN, which is from E. coli N15 phage (paragraph [0213] and Figure 11A).
Regarding claim 3, Scharenberg discloses that the type IIS restriction enzyme can be bspQ1, BbsI, BsaI, BsmBI, BsrDI, EarI, HgaI, or SfaNI (paragraphs [0076] and [0106]). Scharenberg further discloses that the enzyme can be I-SceI (paragraph [0106]).
Regarding claim 7, Scharenberg discloses that the construct can be pUC57 (paragraphs [0200] and [0202]). Scharenberg discloses that selective marker gene (paragraph [0131] and Figure 11A). pUC57 map shows that the vector has both an origin of replication and a selective marker gene (Genscript, map and sequence).
Regarding claim 9, Scharenberg discloses the temperatures at which the contacting steps are performed, which is interpreted as the method being performed at appropriate temperatures for each reaction step (paragraphs [0009]- [0011]).
Regarding claim 12, Scharenberg discloses that the cloning vector can be a pUC57 vector (paragraphs [0200] and [0202]).
Regarding claim 14, Scharenberg discloses that the host cells can be E. coli (paragraph [0215]).
Scharenberg does not explicitly disclose the order of the steps of preparing a target DNA sequence (claims 1 and 11). Scharenberg does not explicitly disclose that there is not a purification step after the first and second cutting reactions (claim 8). Scharenberg fails to explicitly disclose additional restriction endonuclease sites and performing an additional digestion step resulting a double-stranded target DNA fragment having blunt or cohesive ends (claim 15).
However, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to perform the steps of producing a target DNA sequence in any order that includes the culturing of the E. coli host cells, the cutting reactions performed using the protelomerase and the Type IIS restriction enzymes, and the digestion by exonuclease to result in the production of the desired target DNA sequence. Further, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to include additional Type IIS restriction enzyme because this will allow for isolation of the target DNA by using restriction enzymes on either side of the target, resulting in a double-stranded DNA molecule.
It would also have been obvious to one with ordinary skill in the art to perform purification of the target DNA sequence after completing each of the steps of target DNA production. One of ordinary skill in the art would have been motivated to purify the target DNA production after completion of all steps rather than after the first and second cutting reactions in order to reduce the number of steps, possible product loss, and costs.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Scharenberg, as applied to claims 1-3, 7-9, 11-12, and 14-15 above, and in view of Lovett (4(2) EcoSal Plus 10-1128, 1-30 (2011)).
Scharenberg discloses and suggests a method of producing a target DNA sequence, as discussed above.
Scharenberg fails to explicitly disclose the types of exonucleases used in the method.
Regarding claim 6, Lovett discloses that DNA nucleases hydrolyze phosphodiester bonds in DNA from a free end and are important for DNA repair, genetic recombination and mutation avoidance (abstract). Lovett discloses several types of DNA exonucleases from Escherichia coli (page 2, column 1, first paragraph). Lovett discloses that exonucleases include bacteriophage lambda exonuclease (page 5, column 1, second full paragraph). Lovett also discloses Exo T, which is interpreted as being T5 nuclease (Table 1).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to use Lovett’s lambda and T exonucleases in the method of Scharenberg because these are two well-known exonucleases. As such, one of ordinary skill in the art would have had a predictable and reasonable expectation of success is using Lovett’s exonucleases in the method of Scharenberg in order to provide for digestion of nucleotide sequences outside of the target DNA sequence.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Scharenberg, as applied to claims 1-3, 7-9, 11-12, and 14-15 above, and in view of Selmer et al. (PCT Patent Application Publication No. 2008/095927, published August 14, 2008, and cited in the Information Disclosure Statement filed July 21, 2023).
Scharenberg discloses and suggests a method of producing a target DNA sequence, as discussed above.
Scharenberg fails to explicitly disclose inactivation of the enzymes after the cutting reactions.
Selmer discloses a nucleic acid molecule is contacted with a Type IIS restriction endonuclease (abstract and paragraph bridging pages 31 and 32) Selmer discloses after restriction by a Type IIS restriction endonuclease, the Type IIS restriction endonuclease is heat inactivated and a ligase is subsequently added to the reaction (paragraph bridging pages 31 and 32).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to inactivate the enzymes of Scharenberg’s method because, as disclosed by Selmer, this provides for the addition of a later enzyme without interference from the Type IIS restriction endonuclease. One of ordinary skill in the art would have been motivated to inactivated both the protelomerase and the Type IIS restriction endonuclease prior to the next reactions of Scharenberg’s method in order to prevent interference with the enzymes of the previous steps.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Scharenberg, as applied to claims 1-3, 7-9, 11-12, and 14-15 above, and in view of Porter (PCT Patent Application Publication No. WO 2012/017210, published February 9, 2012.
Scharenberg discloses and suggests a method of producing a target DNA sequence, as discussed above.
Scharenberg fails to explicitly disclose the inclusion of a nicking enzyme in the reaction method.
Porter discloses that DNA templates comprising at least one protelomerase target sequence can be amplified (page 22, lines 1-5). Porter discloses that amplification can be initiated from a nicked DNA strand when the template is previously incubated with one or more nicking enzymes (page 22, lines 1-5).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to include Porter’s nicking enzyme in the method of Scharenberg because this provides for an additional place for amplification of the target DNA sequence. One of ordinary skill in the art would have been motivated to include the nicking enzyme in order to provide for amplification of the target sequence.
Allowable Subject Matter
Although not claimed at this time, it is noted that instant SEQ ID NO: 1, the sequence of the cloning vector, appears to be free of the prior art.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Deneke et al. (277(12) The Journal of Biological Chemistry 10410-10419 (2002)) disclose a protelomerase isolated from E. coli prophage N15 (abstract). Deneke et al. disclose that this is the TelN prototelomerase (abstract).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NANCY J LEITH whose telephone number is (313)446-4874. The examiner can normally be reached Monday - Thursday 8:00 AM - 6:30 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, NEIL HAMMELL can be reached at (571) 270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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NANCY J. LEITH
Primary Examiner
Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636
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