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 .
Claim Status
Applicant’s preliminary amendment filed 4/5/2024 has been entered. Claims 1-79, 81, 90-104, 107-115, 117-118, 121, 123, 127-195 are cancelled. Claims 80, 82-89, 105-106, 116, 119-120, 122, 124-126, and 196-198 are pending and examined herein.
Priority
This application is a CON of 18/161,560 (01/30/2023) PAT 11866747; which is a CON of PCT/US2022/025947 (04/22/2022), which has PRO 63/318,192 (03/09/2022), PRO 63/318,191 (03/09/2022), PRO 63/178,263 (04/22/2021), and PRO 63/178,250 (04/22/2021). Accordingly, the EFD is 04/22/2021.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, 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 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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 statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is defective because the file size is listed in KB instead of in bytes.
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 incorporation by reference paragraph, 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.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on page 39. 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.
Drawings
The drawings are objected to for the following reasons: 37 CFR 1.84 (u)(1) states “View numbers must be preceded by the abbreviation "FIG.”
In the current case, the view numbers for Figures 1-53 are preceded by the word "Figure" instead of the abbreviation "FIG.".
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
Claim 126 is objected to because of the following informalities: claim 126 reciting “A genetically-modified eukaryotic cell, or a population of genetically-modified eukaryotic cells, produced the method of claim 80” appears to have a grammatical error missing a preposition between “produced” and “the”. For the purposes of compact prosecution, the claim is interpreted as “produced by the method of claim 80”.
Appropriate correction is required.
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.
Claims 80, 82-89, 105-106, 116, 119-120, 122, 124-126, and 196-198 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 11866747B2 in view of Minczuk et al. (US20210002670A1; published 1/26/2021).
Regarding claims 80, 82, and 126, claims 1 and 5 of the ‘747 patent encompass a polynucleotide sequence comprising a nucleic acid sequence encoding an MTEM, wherein said MTEM binds and cleaves a recognition sequence consisting of SEQ ID NO: 1 in mitochondrial genomes of a eukaryotic cell, wherein said MTEM comprises an engineered meganuclease attached to an MTP, and wherein said engineered meganuclease comprises the amino acid sequence of SEQ ID NO: 9 (see OA.Appendices for Sequence Alignments; instant claim 80).
However, claims 1-24 of the ‘747 patent do not specifically teach the method of producing genetically-modified eukaryotic cells using polynucleotides encoding MTEMs.
Minczuk’s disclosure is directed to targeting and modifying mitochondrial DNA (mtDNA) in eukaryotes with genome engineering tools such as zinc finger nucleases (ZFNs) (entire document).
Regarding claims 80, 82, and 126, Minczuk teaches producing a genetically-modified eukaryotic cell by introducing into a eukaryotic cell one or more polynucleotides comprising ZFNs into a eukaryotic cell for nuclease-mediated genomic modification of an endogenous mitochondrial genome (mutant or wild-type) (paras 0007, 0127-0131). Minczuk teaches methods of reducing or eliminating mutant mitochondrial DNA (mtDNA) in a subject in need thereof (paras 0001 and 0156-0159).
It would have been obvious to one of ordinary skill in the art to have used the polynucleotides encoding the MTEM taught in claims 1-24 of the ‘474 patent to target and degrade mutant mitochondrial genomes, as described by Minczuk because the ‘474 patent and Minczuk teach nuclease-mediated genomic modification of mitochondrial genomes targeting by selective cleavage at targeted recognition sites. Thus, the claimed invention as a whole is prima facie obvious.
Regarding claims 83-89, the limitations are “wherein” clauses that do not add any additional structural limitations. The method made obvious by the ‘747 patent and Minczuk would inherently result in the claimed limitation because it made obvious the claimed method steps and materials recited in the instant claim.
Regarding claims 105 and 106, Minczuk teaches that the recognition sequence is within a region of said mutant mitochondrial genomes associated with a mitochondrial disorder and that the disorder can be Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) (claims 1-10; paras 0011 and 0156-159).
Regarding claim 116, claims 9-21 of the ‘747 patent teach that a recombinant AAV comprises a polynucleotide encoding the claimed MTEM.
Regarding claim 119, claims 13, 17, and 20-21 of the ‘747 patent teaches that the rAAV has an AAV9 capsid.
Regarding claims 120 and 122, claims 12, 14-15, 18-19, and 22-24 of the ‘747 patent teaches that the polynucleotide comprises a promoter operably linked to the nucleic acid sequence encoding MTEM and that the promoter is a CAG promoter.
Regarding claims 124, Minczuk teaches that the eukaryotic cell is a human cell (claim 5; paras 0009, 0028, 0074, and 0079).
Regarding claims 125, Minczuk teaches the human cell can be cardiac cells, brain cells (neuron, astrocyte, microglia), muscle cells, nerve cells, cells of the eye (claim 6, paras 0003, 0010, 0024, and 0027).
Regarding claim 196, claims 2 and 6 of the ‘747 patent teach MTP comprises the amino acid sequence of SEQ ID NO: 45, and wherein said MTP is attached at the N-terminus of said engineered meganuclease (see OA.Appendix for Sequence Alignment).
Regarding claim 197, claims 3-4 and 7-8 of the ‘747 patent teach MTEM is attached to an NES comprising the amino acid sequence of SEQ ID NO: 46, wherein said NES is attached at the C-terminus of said MTEM and said MTEM is attached to a nuclear export sequence (NES) comprising the amino acid sequence of SEQ ID NO: 46, wherein said NES is attached at the C-terminus of said MTEM (see OA.Appendix for Sequence Alignment).
Regarding claim 198, claim 20 of the ‘747 patent teach MTP comprises the amino acid sequence of SEQ ID NO: 45, and wherein said MTP is attached at the N-terminus of said engineered meganuclease, wherein said MTEM is attached to an NES comprising the amino acid sequence of SEQ ID NO: 46, wherein said NES is attached at the C-terminus of said MTEM, wherein said polynucleotide is introduced into said eukaryotic cell by a recombinant AAV comprising said polynucleotide, wherein said recombinant AAV has a serotype of AAV9, and said polynucleotide comprises a promoter operably linked to said nucleic acid sequence encoding said MTEM.
This is a provisional nonstatutory double patenting rejection.
Closest Prior Art
The prior art in Minczuk teaches compositions and methods of targeting and modifying mitochondrial DNA (mtDNA) in eukaryotes with genome engineering tools, such as meganucleases, producing a genetically-modified eukaryotic cell by introducing into a eukaryotic cell one or more polynucleotides (rAAVs) encoding nucleases into a eukaryotic cell for nuclease-mediated genomic modification of an endogenous mitochondrial genome (mutant or wild-type). Minczuk teaches methods treating mitochondrial disorders by reducing or eliminating mutant mitochondrial DNA (mtDNA) in a human subject. However, Minczuk does not specifically teach a mitochondria-targeting engineered meganuclease (MTEM) comprising the amino acid sequence of SEQ ID NO: 9.
SEQ ID NO: 9 sets forth the amino acid sequence of the MIT 25-26x.91 engineered meganuclease having an H to Q substitution at amino acid position 259 referred to as MIT 25-26x.91 259 H>Q.
SEQ ID NO: 9 is required for the method of independent claim 80 and appears to be free of the prior art.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KHALEDA B HASAN whose telephone number is (571)272-0239. The examiner can normally be reached IFP, Monday - Friday 7:30am-5pm.
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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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/KHALEDA B HASAN/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
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