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 .
Applicant’s election without traverse of SEQ ID NO: 782 in the reply filed on December 8, 2025 is acknowledged. However, upon further consideration, the Election of Species Requirement issued October 31, 2025 is withdrawn. Therefore, claims 21-35 will be examined in their entirety.
Information Disclosure Statement
The Information Disclosure Statements filed October 10, 2022 (2) and December 8, 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.
Table 1 contains sequences without sequence identifiers at Column C.
Specification
The use of the terms PIGGYBAC® and PIGGY-BAC® throughout the specification and VI-CELL® at paragraph [00137], 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 21 and 33 are objected to because of the following informalities:
At claim 21, line 4, “ich” should be deleted.
At claim 33, line 1, “comprising” should be changed to “comprises.”
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 21, 26-28, 33-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 16, and 18-21 of U.S. Patent No. 11,060,098.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘098 patent and the instant application claim a method of introducing a transposon into a eukaryotic cell.
Regarding claims 21 and 16, both the ‘098 patent claims a transposon comprising SEQ ID NOS: 7 and 8 flanking a heterologous polynucleotide at left and right ends; introducing a transposase which has a sequence having the sequence of SEQ ID NO: 782 and the ‘098 patent claims a method of using those components to insert a transposon into a eukaryotic cell (claim 1).
Regarding claim 26, both the ‘098 patent and the instant application claim that the cell is a mammalian cell (claim 18).
Regarding claim 27, both the ‘098 patent and the instant application claim that the cell is a human cell (claim 20).
Regarding claim 28, both the ‘098 patent and the instant application claim that the cell is a rodent cell (claim 19).
Regarding claim 33, both the ‘098 patent and the instant application claim that the transposon further includes sequences having at least 90% identity to SEQ ID NOS: 12 and 15 adjacent to the left transposon end between the left transposon and the heterologous polynucleotide and the adjacent to the right transposon and between the right transposon and heterologous polynucleotide, respectively (claim 2).
Regarding claim 34, the ‘098 patent claims that the heterologous polynucleotide comprises two open reading frames, each operably linked to a separate promoter (claim 21).
Therefore the claims of the ‘098 patent anticipate the claims of the instant application.
Claim 22 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 16, and 18-21 of U.S. Patent No. 11,060,098 in view of Morita et al. (8 Molecular Therapy: Methods & Clinical Development 131-140 (2018)).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘098 patent and the instant application claim a method of introducing a transposon into a eukaryotic cell, as discussed above.
The ‘098 patent does not claim that the heterologous polypeptide is a chimeric antigen receptor.
Regarding claim 22, Morita discloses adoptive T cell therapy using a chimeric antigen receptor (CAR) as a promising cancer immunotherapy (abstract). Morita discloses using a piggyBac transposon system to introduce an anti-CD19 CAR into a cell (abstract).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to use the method claimed in the ‘098 patent to produce a chimeric antigen receptor according the Morita because both the ‘098 patent and Morita use a transposon/transposase system to produce a polypeptide. One of ordinary skill in the art would have had a predictable and reasonable expectation of success in producing Morita’s CAR using the ‘098 patent’s claimed method because both use transposons/transposases to produce a polypeptide in a eukaryotic cell.
Claims 23-25 and 35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 16, and 18-21 of U.S. Patent No. 11,060,098 in view of Ley et al. (8(4) PLOS ONE e62784, 1-11 (2013)).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘098 patent and the instant application claim a method of introducing a transposon into a eukaryotic cell, as discussed above.
The ‘098 patent does not claim that the heterologous polypeptide is an antibody. The ‘098 patent does not claim purification of the polypeptide or incorporating the purified polypeptide into a pharmaceutical composition. The ‘098 patent does not claim two polypeptides, which may encode a heavy and light chain of an antibody.
Regarding claim 23, Ley discloses reliable and long term expression of transgenes using a piggyBac transposon vector to produce polypeptides in CHO cells (abstract and page 2, column 1, first full paragraph). Ley discloses expression cassettes comprising heavy or light chains of three therapeutic antibodies (bevacizumab, adalimumab, and rituximab) (paragraph bridging pages 5 and 6).
Regarding claim 24, Ley discloses immunoglobulin concentrations in cell culture, which is interpreted as purifying the polypeptide(s) (page 9, column 2, first full paragraph).
Regarding claim 25, Ley discloses expression cassettes comprising heavy or light chains of three therapeutic antibodies (bevacizumab, adalimumab, and rituximab, which are pharmaceutical compositions for immunotherapy) (paragraph bridging pages 5 and 6).
Regarding claim 35, Ley discloses expression cassettes comprising heavy or light chains of three therapeutic antibodies (bevacizumab, adalimumab, and rituximab) (paragraph bridging pages 5 and 6).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to use the method claimed in the ‘098 patent to produce an antibody as a pharmaceutical composition according the Ley because both the ‘098 patent and Ley use a transposon/transposase system to produce a polypeptide. One of ordinary skill in the art would have had a predictable and reasonable expectation of success in producing Ley’s antibodies using the ‘098 patent’s claimed method because both use transposons/transposases to produce a polypeptide in a eukaryotic cell.
It would also have been obvious to one with ordinary skill in the art to insert sequences encoding both a light and heavy chain of Lay’s antibodies using the method of the ‘098 patent because this will provide a more efficient method of preparing a pharmaceutically acceptable antibody having both a light and heavy chain. One of ordinary skill in the art would be motivated to prepare both light and heavy antibody chains together for increased efficiency and reproducibility.
Claims 21 and 26-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 21-23, 25, and 28-30 of U.S. Patent No. 11,401,521.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘521 patent and the instant application claim a method of integrating a transposon into a eukaryotic cell.
Regarding claim 21, both the ‘521 patent and the instant application claim introducing into the cell a transposon comprising SEQ ID NOS: 7 and 8 flanking a heterologous polynucleotide at left and right ends; introducing a transposase which has a sequence having at least 90% identity to SEQ ID NO: 782 (claim 21).
Regarding claim 26, both the ‘521 patent and the instant application claim that the cell is a mammalian cell (claim 28).
Regarding claim 27, both the ‘521 patent and the instant application claim that the cell is a human cell (claim 30).
Regarding claim 28, both the ‘521 patent and the instant application claim that the cell is a rodent cell (claim 29).
Regarding claim 29, both the ‘521 patent and the instant application claim that the transposase is introduced as a polynucleotide (claim 22).
Regarding claim 30, both the ‘521 patent and the instant application claim that the polynucleotide is an mRNA (claim 23).
Regarding claim 31, both the ‘521 patent and the instant application claim that the transposase is introduced as a protein (claim 24).
Regarding claim 32, both the ‘521 patent and the instant application claim that the transposase has a sequence of SEQ ID NOS: 782 or 805-908 (claim 7).
Therefore the claims of the ‘521 patent anticipate the claims of the instant application.
Claim 22 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 21-23, 25, and 28-30 of U.S. Patent No. 11,401,521 in view of Morita et al. (8 Molecular Therapy: Methods & Clinical Development 131-140 (2018)).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘521 patent and the instant application claim a method of introducing a transposon into a eukaryotic cell, as discussed above.
The ‘521 patent does not claim that the heterologous polypeptide is a chimeric antigen receptor. The ‘521 patent does not claim purification of the polypeptide or incorporating the purified polypeptide into a pharmaceutical composition.
Regarding claim 22, Morita discloses adoptive T cell therapy using a chimeric antigen receptor (CAR) as a promising cancer immunotherapy (abstract). Morita discloses using a piggyBac transposon system to introduce an anti-CD19 CAR into a cell (abstract).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to use the method claimed in the ‘521 patent to produce a chimeric antigen receptor according the Morita because both the ‘521 patent and Morita use a transposon/transposase system to produce a polypeptide. One of ordinary skill in the art would have had a predictable and reasonable expectation of success in producing Morita’s CAR using the ‘521 patent’s claimed method because both use transposons/transposases to produce a polypeptide in a eukaryotic cell.
Claims 23-25 and 34-35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 21-23, 25, and 28-30 of U.S. Patent No. 11,401,521 in view of Ley et al. (8(4) PLOS ONE e62784, 1-11 (2013)).
The ‘521 patent does not claim that the heterologous polypeptide is an antibody. The ‘098 patent does not claim purification of the polypeptide or incorporating the purified polypeptide into a pharmaceutical composition. The ‘521 patent does not claim two polypeptides, which may encode a heavy and light chain of an antibody.
Regarding claim 23, Ley discloses reliable and long term expression of transgenes using a piggyBac transposon vector to produce polypeptides in CHO cells (abstract and page 2, column 1, first full paragraph). Ley discloses expression cassettes comprising heavy or light chains of three therapeutic antibodies (bevacizumab, adalimumab, and rituximab) (paragraph bridging pages 5 and 6).
Regarding claim 24, Ley discloses immunoglobulin concentrations in cell culture, which is interpreted as purifying the polypeptide(s) (page 9, column 2, first full paragraph).
Regarding claim 25, Ley discloses expression cassettes comprising heavy or light chains of three therapeutic antibodies (bevacizumab, adalimumab, and rituximab, which are pharmaceutical compositions for immunotherapy) (paragraph bridging pages 5 and 6).
Regarding claim 35, Ley discloses expression cassettes comprising heavy or light chains of three therapeutic antibodies (bevacizumab, adalimumab, and rituximab) (paragraph bridging pages 5 and 6).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to use the method claimed in the ‘521 patent to produce an antibody as a pharmaceutical composition according the Ley because both the ‘521 patent and Ley use a transposon/transposase system to produce a polypeptide. One of ordinary skill in the art would have had a predictable and reasonable expectation of success in producing Ley’s antibodies using the ‘521 patent’s claimed method because both use transposons/transposases to produce a polypeptide in a eukaryotic cell.
It would also have been obvious to one with ordinary skill in the art to insert sequences encoding both a light and heavy chain of Lay’s antibodies using the method of the ‘521 patent because this will provide a more efficient method of preparing a pharmaceutically acceptable antibody having both a light and heavy chain. One of ordinary skill in the art would be motivated to prepare both light and heavy antibody chains together for increased efficiency and reproducibility.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Kasahara et al. (447 Nature 714-719 (2007), and cited in the Information Disclosure Statement filed December 8, 2025) disclose the assembled medaka genome of about 700 megabases (abstract). Kasahara et al. disclose that medaka, a teleost, is an excellent model system for a wide range of biology, including ecotoxicology, carcinogenesis, and sex determination (abstract). While Kasahara et al. does disclose the entire medaka sequence, which includes the instant application’s SEQ ID NO: 782, Kasahara et al. do not disclose the specific sequence, the sequence as being a transposase, or any transposases at all, or sequences thereof.
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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NANCY J. LEITH
Primary Examiner
Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636