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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 1/13/2026 has been entered.
Applicant’s amendment of claim 1, 3-11, 24, 27, in the paper of 71/13/2026, is acknowledged. Applicants' arguments filed on 1/13/2026, have been fully considered and are deemed to be persuasive to overcome some of the rejections previously applied. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. Claims 1, 3-11, 24-31 are still at issue and are present for examination.
Election/Restrictions
Applicant's election without traverse of Group I, claims 1-29 and 32 drawn to a mutant Taq DNA polymerase, classified in C12N 9/1252, in the paper of 4/13/2023, is acknowledged. Applicant's election with traverse of the Species Group 1 species: substitution of amino acid 784 of SEQ ID NO:1 and Species Group 1 species: SEQ ID NO:85, in the paper of 4/13/2023, is acknowledged.
Applicants previous traversal of the previous species election in the paper of 4/13/2023, is acknowledged and has been carefully considered, however, is found non-persuasive for the reasons communicated to applicants representative in the previous interview summary of 1/9/2024.
As stated in the interview summary, Applicants election with traverse of the substitution of amino acid 784 of SEQ ID NO:1 as the species of Group 1 and SEQ ID NO:85 as the species of Group 2 was acknowledged. In response to applicants submission that the examiner would not be overburdened in searching and examination of SEQ ID NO:174 in addition to elected SEQ ID NO:85 because SEQ ID NO:85 is a truncated version of SEQ ID NO:174, this is not found persuasive on the basis that while SEQ ID NO:85 may be a fragment of SEQ ID NO:174, they are still two separate and distinct amino acid sequences. Depending what the patentable invention is the determination of the allowability of the elected species (SEQ ID NO:85) may also relate to the non-elected species (SEQ ID NO:174) at which time the non-elected species may be withdrawn. Prior to such a determination the species are still independent and distinct. Thus the examination and search of the additional species of SEQ ID NO:174 would present an undue burden on the examiner. Further applicants traversal that the species election requirement is improper on the basis that the Examiner has already conducted the relevant search and examination of SEQ ID NO:85 and SEQ ID NO:174 during prosecution of the parent case, is not found persuasive as the issued parent patent US 10,982,247, is NOT drawn to a mutant polymerase but rather but to a method of conducting primer extension and thus the relevant search has NOT already been done. Further applicants traversal that the species election requirement is improper on the basis that the Examiner has already conducted a search for SEQ ID NO:1 having a 784 amino acid substitution and the Examiner would not be overly burdened by extending his search for SEQ ID NO:1 having a 783 amino acid substitution or a SEQ ID NO:1 having a 783/784 double amino acid substitution is not found persuasive, as the additional mutation positions would cause a further burden on the search and examination. Applicant's request for rejoinder of Group I and II inventions is acknowledged as is the potential rejoinder of additional species and will be considered at the time of the identification of allowable subject matter.
Claims 30 and 31 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claim Objections
Claims 24, 27 and 29 are objected to because of the following informalities:
Claims 24 and 27 each recite “a fusion protein according to claim 1” while the claims 3-11 each recite “a fusion protein according to claim 1”. It is suggested that applicants maintain consistency throughout the claims.
Claim 29 depends from rejected claim 27.
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 4-11 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.
Claims 4-11 each recites the limitation "the enhanced template discrimination activity" in claim 1. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 102
The rejection of claim(s) 1-11, 12-23, 24-29 under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Efcavitch et al. (U.S. 2010/0203524, pub date Aug. 12, 2010) is withdrawn based upon applicants amendment of the claims and arguments presented in the paper of 12/26/2023 .
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 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 rejection of claims 1-11, 12-23, 24-29 under 35 U.S.C. 103 as being unpatentable over Efcavitch et al. (U.S. 2010/0203524, pub date Aug. 12, 2010) as applied to claims 1-11, 12-23, 24-29 above, and further in view of Dobosy et al. (BMC Biotechnology 2011, 11:80, pp 1-18) is withdrawn based upon applicants amendment of the claims and arguments presented in the paper of 12/26/2023.
The rejection of claims 1, 3-11, 24-28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Efcavitch et al. (U.S. 2010/023524, pub date Aug. 12, 2010) and further in view of Brandis et al. (US 6,265,193) as evidenced by Lawyer et al. (Uniprot Accession No P19821, Feb 1991) is withdrawn based upon applicants amendment of the claims and arguments presented in the paper of 1/13/2026.
.
Claims 1, 3-11, 24-28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Efcavitch et al. (U.S. 2010/0203524, pub date Aug. 12, 2010), Brandis et al. (US 6,265,193) and Hanzel et al. (US 2007/0196846) as evidenced by Lawyer et al. (Uniprot Accession No P19821, Feb 1991)
As stated previously, Efcavitch et al. teach polymerases for efficient and controlled sequencing-by-synthesis reactions and methods of their use in nucleic acid synthesis methods. Efcavitch et al. teach a number of polymerase enzymes including at least one mutation that enhances ability of the polymerase as compared to a wild-type polymerase to incorporate a nucleotide into a nascent strand of DNA or cDNA including at least one modified nucleotide. Efcavitch et al. teach a mutant Taq DNA polymerase having the amino acid sequence of the Taq DNA polymerase and a H784Q substitution (see claim 9 and paragraphs [0009] , [0010], [0030]…). Efcavitch et al. teach that the mutant Taq DNA polymerase having a H784Q substitution has an enhanced ability to incorporate a nucleotide into a nascent strand of DNA or cDNA comprising at least one modified nucleotide.
Efcavitch et al. also teach kits or compositions comprising the above mutant polymerase and hybridizable primers, nucleoside triphosphates, buffer and a blocked primer. Efcavitch et al. teach a mutant Taq DNA polymerase comprising a H784Q substitution and they teach that the mutant has an enhanced ability compared to the wild-type polymerase to incorporate a nucleotide into a nascent strand of DNA comprising a modified nucleotide. Efcavitch et al. teach the above mutant Taq DNA polymerase comprising the SEQ ID NO:85 and the corresponding KlenTaq polymerase mutant of H784Q [SEQ ID NO:174]. Thus Efcavitch et al. teach a method for conducting primer extension (nucleic acid synthesis), comprising: contacting a mutant DNA polymerase with a primer, a polynucleotide template, and nucleoside triphosphates under conditions suitable for a primer extension method, thereby producing an extended primer, wherein the mutant DNA polymerase is a mutant Taq DNA polymerase having the amino acid sequence of the Taq DNA polymerase and a H784Q substitution. While Efcavitch et al. may not measure the polymerase activity of the taught mutants a listed in applicants dependent claims, this activity is considered inherent to the polymerase mutant taught by Efcavitch et al. based upon the high level of sequence identity to the instant mutant Taq DNA polymerase.
Efcavitch et al. further teach and claim a polymerase comprising at least one mutation that enhances ability of the polymerase to incorporate a nucleotide into a DNA strand in a Taq DNA polymerase. Efcavitch et al. further teach the above mutant Taq DNA polymerase comprising the mutations H784Q and T664A.
Brandis et al. teach DNA polymerases having improved labeled nucleotide incorporation properties, specifically reduced discrimination against labeled nucleotides. Brandis et al. teach DNA polymerases which have at least one mutation in the nucleotide label interaction region of the enzyme such that it results in reduced discrimination against labeled nucleotides. Brandis et al. teach that the nucleotide interaction region is located at portions of the O-helix, K-helix and the outer O-P helical loop of Taq DNA polymerase. Brandis et al. teach a DNA polymerase having at least one mutation as defined with respect to a naturally occurring DNA polymerase wherein the mutation is at an amino acid position H784 of Taq DNA polymerase and the DNA polymerase has at least two-fold reduced discrimination for a fluorescein-type dye labeled nucleotide as compared with the naturally occurring DNA polymerase and kits comprising said polymerases, and nucleic acid primers.
While both Efcavitch et al. and Brandis et al. reference the wild type sequence of Taq DNA polymerase, they do not actually disclose the sequence of the wild type DNA polymerase. Lawyer et al. (Uniprot Accession No P19821, Feb 1991) disclose the amino acid sequence of the wild-type Taq DNA polymerase as comprising 832 amino acids that are identical to instantly disclosed SEQ ID NO:85, with the single exception of a substitution at position H784 of “Q” or glutamine.
Hanzel et al. (US 2007/0196846) teach polymerases for nucleotide analogue incorporation and methods of using said polymerases for synthesizing polynucleotides (see claims and supporting text). Hanzel et al. further teach fusion proteins comprising the taught polymerases and one or more affinity tag or sequence for binding the polymerase to a surface. Hanzel et al. teach that in general these surface binding elements and purification tags that can be added to the polymerase include e.g., polyhistidine tags, HIS-6 tags, biotin, avidin, GST sequences, BiTag sequences, S tags, SNAP-tags, enterokinase sites, thrombin sites, antibodies or antibody domains, antibody fragments, antigens, receptors, receptor domains, receptor fragments, ligands, dyes, acceptors, quenchers, or combinations thereof.
One of skill in the art before the effective filing date of the claimed invention would have been motivated to create and use a mutant Taq DNA polymerase comprising a H784Q mutation as taught by Efcavitch et al. and Brandis et al., in the Taq DNA polymerase sequence as evidenced by Lawyer et al. as a means of eliciting the effect on the discrimination of nucleotide analogs incorporation into a synthesized DNA. The obvious mutant Taq DNA polymerase would consist of the amino acid sequence of the wild type Taq DNA polymerase with a H784Q substitution which is the same as that Taq DNA polymerase consisting of the amino acid sequence of SEQ ID NO:85. As Efcavitch et al. further teach mutant Taq DNA polymerases comprising the mutations H784Q and T664A in the Taq background and Brandis et al. teach Taq DNA polymerase comprising a H784 substitution, one of skill would have been further motivated to create mutant Taq polymerases comprising only the single H784Q and only the singleT664A substitution in the Taq polymerase background as means of understanding the relationship of each mutant to the other and any altered functionality. One of skill in the art before the effective filing date would have been further motivated to fuse an affinity or purification tag to the amino terminal to the above obvious Taq DNA polymerase consisting of the amino acid sequence of SEQ ID NO: 85 as a means of isolating the mutant Taq DNA polymerase as taught by Hanzel et al. and to include the polymerase as a part of a reaction mixture and kit comprising said polymerases, and nucleic acid primers in separate containers. It is noted that claims 3-11 are included in the rejection on the basis that the DNA polymerase activity limitations of claims 3-11 are considered inherent to the polymerase of claim 1 which consists of SEQ ID NO:85, based on the identical structure of that which is obvious and that which is claimed. The expectation of success is high based upon the level of skill in the art as exemplified by the results of Efcavitch et al. and Brandis et al. who teach mutant DNA polymerase comprising a H784Q substitution and how to make such mutant DNA polymerases.
Applicants Response:
Applicants comments regarding the previous rejection over Efcavitch et al. (U.S. 2010/023524, pub date Aug. 12, 2010) and further in view of Brandis et al. (US 6,265,193) as evidenced by Lawyer et al. (Uniprot Accession No P19821, Feb 1991 were considered to the extent they apply to the above rejection. These comments were not found persuasive in overcoming the above rejection.
Remarks
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RICHARD G HUTSON whose telephone number is (571)272-0930. The examiner can normally be reached 6-3 EST Mon-Fri.
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rgh
3/4/2026
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652