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 .
Application Status
The amendments and remarks filed 03 November 2023 have been entered. Claim 4 has been amended. Claims 1-23 are pending and being examined on the merits.
Priority
This application claims priority to applications 63/335,625 filed 4/27/2022 and 63/433,353 filed 12/16/2022.
Information Disclosure Statement
This information disclosure statement filed 1/31/2024 has been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on page 46. 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.
Claim Rejections - 35 USC § 112
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 15 and 18 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. Claims 15 and 18 recite “wherein the DNA polymerase protein comprises the segment of the MS2 bacteriophage coat protein” and depends from claim 4 which already requires that the DNA polymerase protein comprises the segment of the MS2 bacteriophage coat protein. Therefore, the claims fail to further limit the subject matter of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies 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.
Claims 1-2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Goodman (US 5945312, published 8/31/1999).
Regarding claims 1-2, Goodman teaches the mutant T4 DNA polymerase D219A [Col. 7, lines 31-39]. A fusion protein comprising a DNA polymerase protein and a segment of an MS2 bacteriophage coat protein is optional and therefore is required for claim 1.
Claims 1-2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yang 2002 (Yang et al. Biochemistry 2002, 41, 2526-2534).
Regarding claims 1-2, Yang 2002 teaches the D222A mutant RB69 DNA polymerase [pg. 2527, col. 2, para 2].
Claims 1-3 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yang (Yang et al. Nucleic acids research. , 2019, Vol.47, p.7402).
Regarding claims 1-3, Yang teaches that T4 and RB69 DNA mutant polymerases (T4-D219A and RB69-D222A) are capable of improving CasPlus editing efficiency [pg. 5, last paragraph – pg. 6, para 1]. A fusion protein comprising a DNA polymerase protein and a segment of an MS2 bacteriophage coat protein is optional and therefore is required for claim 1.
Claims 1-3 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hogg (Hogg et al. Nucleic Acids Research, 2006, Vol. 34, No. 9).
Regarding claims 1-3, Hogg teaches exonuclease mutants T4 and RB69 DNA polymerases (D219A and D222A) [pg. 2529; col. 2, para 1-2]. Hogg teaches that these polymerases exhibit much higher proper base pairing than improper base paring [comparing Fig. 3 with that of Fig. 2 and 4]. Hogg also teaches that there are high sequence identity between T4 and RB69 [pg. 2533, col. 1, para 2] however they different abilities to form various base parings [pg. 2534, col. 1, para 3]. A fusion protein comprising a DNA polymerase protein and a segment of an MS2 bacteriophage coat protein is optional and therefore is required for claim 1.
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, 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 1-5 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Maresca (WO 2021/204877) in view of Hogg (Hogg et al. Nucleic Acids Research, 2006, Vol. 34, No. 9).
Regarding claims 1-5, Maresca teaches proteins, compositions, methods, and kits for improved gene editing efficiency [abstract]. Maresca teaches a fusion protein comprising: (i) a Cas nuclease and (ii) a reverse transcriptase (RT), a DNA polymerase, a DNA ligase, or a combination thereof, wherein the Cas nuclease is capable of generating a double-stranded polynucleotide cleavage [0004]. Maresca teaches where the fusion protein further comprises the RNA-binding domain MS2 coat protein (MCP2) [0010, 00212]. Maresca teaches that the MCP domains bind to MS2 aptamers which was fused to the template for reverse transcription (RT template) and that a DNA sequence was successfully copied and inserted specifically from MS2-RT template by a Cas9-MCP-RT [00213].
Maresca does not teach where the DNA polymerase is the T4 or RB69 DNA mutant polymerases of T4-D219A and RB69-D222A.
Regarding claims 1-5, Hogg teaches exonuclease mutants T4 and RB69 DNA polymerases (D219A and D222A) [pg. 2529; col. 2, para 1-2]. Hogg teaches that these polymerases exhibit much higher proper base pairing than improper base paring [comparing Fig. 3 with that of Fig. 2 and 4]. Hogg also teaches that there are high sequence identity between T4 and RB69 [pg. 2533, col. 1, para 2] however they different abilities to form various base parings [pg. 2534, col. 1, para 3].
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the DNA polymerase in the fusion protein of Maresca with the T4-D219A or RB69-D222A polymerase of Hogg. One of ordinary skill would be motivated to make the modification for the advantage of decreasing base pairing error rate during genome editing.
Regrading claim 12, Maresca teaches a method for introducing vectors comprising the fusion protein and guide RNA into eukaryotic cells to create indels [Fig. 15; 0002; 0036; 0075; 0079; 00160; 00190-00191]
Claims 5-11, 13-18 are rejected under 35 U.S.C. 103 as being unpatentable over Maresca (WO 2021/204877) in view of Hogg (Hogg et al. Nucleic Acids Research, 2006, Vol. 34, No. 9) and applied to claims 1, 4, 5, and 12 and further in view of Shanghai (CN106987571A, published 7/28/2017).
The teachings of Maresca and Hogg are discussed above as applied to claims 1, 4, 5, and 12, and similarly apply to claims 5-6, 9-11, 13-18.
Maresca and Hogg do not teach where the Cas9 comprises the mutation of F916P.
Regarding claims 5-6 and 9, Shanghai teaches a Cas9-F916P nuclease, and that using the Cas9-F916P to cut the DNA double strand can produce a protruding broken end, and the base that is complementary to the protruding broken end can be added through the cell's self-repair system to fill in the connection, which can realize genomic DNA Precise editing of specific bases added to specific positions of the fragment [pg. 3, para 1].
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to further modify the system as taught and suggest by Maresca and Hogg by substituting the Cas9 nuclease in the fusion protein with the Cas9-F916P nuclease of Shanghai. One of ordinary skill would be motivated to make the modification for the advantage of generating a specific genome editing system that can produce genomic DNA Precise editing of specific bases.
Regarding claim 7, Maresca teaches where the composition comprises the use of a guide sequence for the insertion of a DNA sequence without a repair template [0036-0037].
Regarding claim 8, the teachings of Maresca are discussed above as applied to claims 1 and 4.
Regarding claim 10, the teachings of Maresca and Shanghai are discussed above as applied to claims 7 and 9.
Regarding claim 11, the teachings of Maresca and Shanghai are discussed above as applied to claims 1, 4-5, 9, and 10.
Regarding claim 13 and 14, the teachings of Maresca and Shanghai are discussed above as applied to claims 1, 4-6 and 12. It is noted that the guide is to “optionally” require the MS2 coat protein.
Regarding claim 15, the teachings of Maresca and Shanghai are discussed above as applied to claims 1, 4-6 12 and 13.
Regarding claim 16 and 17, the teachings of Maresca and Shanghai are discussed above as applied to claims 1, 3-5 and 12.
Regarding claim 18, the teachings of Maresca and Shanghai are discussed above as applied to claims 1, 4, 12 and 16-17.
Claims 19-23 are rejected under 35 U.S.C. 103 as being unpatentable over Maresca (WO 2021/204877) in view of Hogg (Hogg et al. Nucleic Acids Research, 2006, Vol. 34, No. 9) and applied to claims 1, 4, 5, and 12 and further in view of Zhang (US 2020/0190487 A1).
The teachings of Maresca and Hogg are discussed above as applied to claims 1, 4, 5, and 12, and similarly apply to claims 19-23.
Maresca and Hogg do not teach where the indel corrects a mutation in a gene associated with muscular dystrophy or cystic fibrosis, where the eukaryotic cells leukocytes are T cells, where the indel is in one or more of PDCD1, TRBC1, TRBC2, or TRAC, or where the T cells are also modified such that they express a chimeric antigen receptor (CAR).
Zhang teaches systems, methods and compositions used for targeted gene modification, targeted insertion, perturbation of gene transcripts, nucleic acid editing using novel nucleic acid targeting systems that comprise components of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) systems and transposable elements [abstract].
Regarding claim 19, Zhang teaches the use of the CRISPR system in a method for therapy in which cells are edited by the system to modulate as least one gene by knocking in, knocking out, or knocking down expression of at least one gene in a cell [0836]. Zhang teaches the correction of a mutation is a gene from a disorder or condition [0920-0921] Zhang teaches where the treatment is for a disease or disorder such as muscular dystrophy [0849] and Cystic Fibrosis [0852; 1072-1077].
Regarding claims 20-21 and 23, Zhang teaches that the system can be used to modify cells for adoptive therapy such as T cells and CAR-T cells [1091, 1093].
Regarding claim 22, Zhang teaches the system can be used to alter one or more T-cell expressed gene such as the PDCDI and/or TRAC and/or TRBC gene [0925].
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to further modify the method as taught and suggest by Maresca and Hogg where the indel corrects a mutation in a gene associated with muscular dystrophy or cystic fibrosis, where the eukaryotic cells leukocytes are T cells, where the indel is in one or more of PDCD1, TRBC1, TRBC2, or TRAC, or where the T cells are also modified such that they express a chimeric antigen receptor (CAR). The combination of prior art elements according to known methods to yield predictable results supports can support a conclusion of obviousness. See MPEP 2143(I). One of ordinary skill in the art would have a reasonable expectation of success since both Maresca and Zhang teach the use of CRISPR Cas systems to edit genomes of a cell.
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.
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Claims 1-2, 4-8, 10-15, and 17-23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 7, and 10 of copending Application No. 18251384 in view of Maresca (WO 2021/204877), Hogg (Hogg et al. Nucleic Acids Research, 2006, Vol. 34, No. 9), Shanghai (CN106987571A, published 7/28/2017) and Zhang (US 2020/0190487 A1).
The patent claims all limitations of claim 1 except, where the T4 DNA polymerase comprises the mutation of D219A. The teachings of Hogg are discussed above. It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the DNA polymerase in the fusion protein of patent a with the T4-D219A polymerase of Hogg. One of ordinary skill would be motivated to make the modification for the advantage of decreasing base pairing error rate during genome editing.
For additional limitations of the instant claims, see the additional teachings of the patented claims. To the extent that there are limitations that are not provided for by the patented claims, the teachings of Maresca, Hogg, Shanghai and Zhang are discussed above. It would have been obvious to have modified the subject matter of the patented claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims allowed.
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/TIFFANY NICOLE GROOMS/Examiner, Art Unit 1637