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
Claims 1-16 are pending.
Drawings
The drawings are objected to because Figures 1-3 and 5 each contain grayscale renditions of color drawings that are not possible to interpret. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 4-16 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, claims 4-16 have not been further treated on the merits.
Election/Restrictions
Applicant’s election without traverse of the species comprising substitutions A451F and S636F relative to SEQ ID NO: 2. in the reply filed on 7/2/2026 is acknowledged.
Search of Applicant’s elected species did not result in prior art, so all substitutions recited in claims 1-3 were searched.
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 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 isolated polypeptide comprises at least one amino acid substitution selected from the group consisting of G12, K114…N574L. N574L is a specific amino acid substitution, not a position, thus it is unclear, at position 574, whether the amino acid substitution from asparagine (N) to leucine (L), or a substitution from asparagine (N) to any other amino acid, is required.
Claims 1-2 each recite a position Q565 relative to SEQ ID NO: 2. However, position 565 of SEQ ID NO: 2 is E, not Q. Therefore, claims 1-2 are indefinite.
Claim 3 recites E590Y relative to SEQ ID NO: 2. However, the amino acid residue at position 590 is glutamine (Q), thus the metes and bounds of the claim are undefined as it is unclear whether the substitution occurs at position 590 or at a position in which the original amino acid is glutamic acid (E).
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 1-3 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 claims 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 is drawn to an isolated polypeptide having a DNA polymerase activity comprising an amino acid sequence having at least 75% sequence identity to amino acids 11-739 of SEQ ID NO: 2 and comprising at least one amino acid substitution relative to SEQ ID NO: 2 at a position selected from the group consisting of G12, K114, L117, N194, M232, N298, G313, A451, K490, L538, P542, Q565, I570, N574L, Q590, E633, S636, E639, K655, and D681. Claims 2-3 further limit the amino acid substitutions.
The person of ordinary skill in the art would not have recognized that the inventors, at the time the application was filed, had possession of the claimed genus of DNA polymerase variants with at least 75% identity to amino acid residues 11-739 of SEQ ID NO: 2. A variant with at least 75% identity to amino acid residues 11-739 of SEQ ID NO: 2 differs by up to 182 amino acids from SEQ ID NO: 2 (25% of 728).
The specification discloses a Pol6 variant, Pol6-1743, comprising the following substitutions relative to SEQ ID NO: 2: T529M, S366A, A547F, N545L, Y225L, D657R, K561G, K541R, T544A, S692Y, V299R, E680Q, Y242A, E585K, Vl64K, F528Y, N635R, E534R, P523F, Q221K, and K682Y ([00103]). Therefore, Pol6-1743 differs by 21 amino acids and is 97% similar to residues 11-739 of SEQ ID NO: 2. The specification discloses 33 single substitution variants of Pol6-1743 ([00105], [00109]). Further single amino acid substitutions are made to these variants in the table presented in [00116]. However, since these variants only introduce single amino acid substitutions, the total number of mutations relative to SEQ ID NO: 2 is still on the order of 21-23 substitutions. The effect of combinations of the substitutions on DNA polymerase activity would not have been predictable.
Boenitz et al. (WO 2018/054970 A2) teaches a DNA polymerase comprising mutations (Table 3 on page 44). The majority of the variants comprise single amino acid substitutions, although one species (Y225T/S366A/T647F/K573M/L576M) has five amino acid substitutions. Boenitz also exemplifies a pol6 DNA polymerase variant with the mutations T529M+S366A+A547F+N545L+Y225L+D657R+K561G+K541R+ T544A+S692Y+Y242A+E585K ([0130]). Boenitz performs site-directed mutagenesis of the pol6 DNA polymerase at rational positions to impact Pol6-nucleotide binding identified based on homology modeling of known crystal structures ([0097]).
Volozhantsev et al. (PloS one 7.5 (2012): e38283) teaches the isolation of the bacteriophages ՓCPV4, ՓZP2, and ՓCP7R (Abstract). The instant DNA polymerase having SEQ ID NO: 2 is from ՓCPV4 (instant specification [0064]). Volozhantsev teaches that ՓCPV4 has a predicted type B polymerase that is 99% similar to the polymerase from ՓCP7R and 96% similar to the polymerase from ՓZP2 (page 3, left column, paragraph 1). However, these three phages are only 36% similar in sequence to the polymerase from ՓCPV1 (page 3, left column, paragraph 1). The ՓCPV4, ՓZP2, and ՓCP7R DNA polymerase proteins contained a consensus sequence of Dx2SSYP rather than the Dx2SLYP with the intervening x2 being IN rather than VN as found in the Փ29 polymerase motif A (page 3, right column, paragraph 1). The two Asp (D) residues that participate in metal binding required for catalysis are located in the conserved motif C sequence identical to the Փ29 polymerase (page 3, right column, paragraph 1).
To summarize, although the prior art teaches several species of DNA polymerase variants, these variants differ by far fewer than 182 amino acids relative to SEQ ID NO: 2. In other words, they are highly similar to SEQ ID NO: 2 and the amino acid sequences of these variants do not approach the lower bound of the claimed range of at least 75% similar to SEQ ID NO: 2. The prior art also teaches limited structure-function information regarding the DNA polymerase pol6 (SEQ ID NO: 2).
Based on the above analysis, the person of ordinary skill in the art would not have recognized that the inventors, at the time the application was filed, had possession of the claimed genus of DNA polymerase variants with at least 75% identity to amino acid residues 11-739 of SEQ ID NO: 2.
Claim Rejections - 35 USC § 102
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 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.
Claims 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Boenitz et al. (WO 2018/054970 A2).
Boenitz teaches a DNA polymerase comprising amino acid substitutions at N298, L538, P542, E639, and K655 of SEQ ID NO: 2, which is Pol6 with a His tag ([009]). SEQ ID NO: 2 of Boenitz is 97.7% identical to the amino acid residues 11 to 739 of the instant SEQ ID NO: 2 (Sequence alignment in OA Appendix A).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 12 of U.S. Patent No. 10,829,747 (hereafter ‘747). Although the claims at issue are not identical, they are not patentably distinct from each other because instant claim 1 is anticipated by claim 12 of ‘747.
Claim 12 recites an isolated polypeptide comprising at least 90% sequence identity to SEQ ID NO: 1 comprising substitutions T529M+S366A+A547F+N545L+Y225L+D657R+K561G+K541R+T544A+S692Y +D693P+V299F relative to SEQ ID NO: 2 further comprising the amino acid substitution K655G/W (embodiment (A)(cc)), N298G (embodiment (D)(f)) or L538A (embodiment (D)(r)). SEQ ID NO: 1 of ‘747 is identical to the amino acid residues 11 to 739 of the instant SEQ IDN O: 2 (OA Appendix B).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CANDICE LEE SWIFT whose telephone number is (571)272-0177. The examiner can normally be reached M-F 8:00 AM-4:30 PM (Eastern).
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/CANDICE LEE SWIFT/Examiner, Art Unit 1657
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