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 .
This action is in response to the amendment, filed 08/27/2025, in which claims 4-7, 13, 15, 62 were cancelled; claims 1, 8-9 were amended. Applicant’s arguments have been thoroughly reviewed, but are not persuasive for the reasons that follow. Any rejections and objections not reiterated in this action have been withdrawn. This action is FINAL.
Election/Restrictions
Applicant's election with traverse of Group I and the species of (A) an artificial CRE recognizing histone tails with specific methylated sites; (B) a single chain antibody; (C) a hyperactive PiggyBac transposase; and (D) a polynucleotide encoding a polypeptide antibody; (C) a hyperactive PiggyBac transposase; and (D) a polynucleotide encoding a polypeptide.in the reply filed on 08/27/2025 is acknowledged. The traversal is on the ground(s) that claim 1 is drawn to a polypeptide comprising a transposase and at least one heterologous histone reader domain. Applicant contends that this polypeptide is the inventive technical feature commonly shared among all pending claims. This is not found persuasive because:
Cordeaux et al. (Birth of a chimeric primate gene by capture of the transposase gene from a mobile element. PNAS, May, 2006) teaches that SETMAR, a new primate chimeric gene resulting from fusion of a SET histone methyltransferase gene to the transposase gene of a mobile element; showing that the transposase gene was recruited (reads on heterologous) as part of SETMAR 40–58 million years ago, after the insertion of an Hsmar1 transposon downstream of a preexisting SET gene (e.g., abstract).
Therefore, indicating lack of unity of invention between Groups I, II, III and IV as stated in Requirement for Restriction/Election filed 11/06/2024.
The requirement is still deemed proper and is therefore made FINAL.
Priority
The application is a continuation of a 371 of application PCT/EP2019/053571 filed February 13 2019 is acknowledged.
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 #1 – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. See Fig. 6B.
Claim Objections
Claims 8-9, 39, 51 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Rejections withdrawn
The rejection of claims 4-7, 13, 15-16 and 62, under 35 U.S 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as falling to comply with written description, is moot in view of Applicant’s cancellation of the claims in the reply in the reply filed 08/27/2025.
The rejection of claims 1, 39, 51, under 35 U.S 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as falling to comply with written description, has been withdrawn in view of Applicant’s amendments to the claim in the reply in the reply filed 08/27/2025.
The rejection of claims 4-5, 7, 13, 16 and 62 under 35 U.S 102(a)(1), is moot in view of Applicant’s cancellation of the claims in the reply in the reply filed 08/27/2025.
The rejection of claims 1, 39, 51, 59 under 35 U.S 102(a)(1), has been withdrawn in view of Applicant’s amendments and arguments to the claims in the reply in the reply filed 08/27/2025.
The rejection of claims 8-9, under 35 U.S 103 has been withdrawn in view of Applicant’s amendments of the claims in the reply in the reply filed 08/27/2025.
New Rejection necessitated by Claim Amendment
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.
Claim 1 contains the trademark/trade name PiggyBac. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a transposase and, accordingly, the identification/description is indefinite.
This rejection is made to address the amendment to the claim in the reply filed 08/27/2025.
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.
Claim 59 is 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 claim(s) 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. This rejection is maintained.
Claim 59 recites a kit comprising (i) a transposable element comprising a cloning site for inserting at least one polynucleotide of interest, and (ii) at least one heterologous histone reader element and a polypeptide comprising an active transposase or a fragment or a derivative thereof having transposase function. The critical essential elements are the transposase and histone reader element or domain; however, the claims are not limited to any particular transposase or histone reader element, the claims do not specify what type of transposase or histone reader element.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof.
The specification envisions a polypeptide comprising a transposase or a fragment or a derivative thereof having transposase function and at least one heterologous chromatin reader element (CRE). The specification envisions a method for producing a transgenic cell comprising the steps of: (i) providing a cell, and (ii) introducing a transposable element comprising at least one polynucleotide of interest, and a polypeptide according to the first aspect, a polynucleotide according to the second aspect, or a vector according to the third aspect into the cell, thereby producing/obtaining the transgenic cell. The specification envision the use of a transgenic cell according to the fifth aspect for the production of a protein or virus. The chromatin reader domain (CRD) recognizing histone methylation degree is a plant homeodomain (PHD) type zinc finger, or the (naturally occurring) CRD recognizing the acetylation state of histones is a bromodomain. Most preferably, the PHD type zinc finger is a transcription initiation factor TFIID subunit 3 PHD, e.g. having an amino acid sequence according to SEQ ID NO: 20; or the bromodomain is a histone acetyltransferase domain, like a histone acetyltransferase KAT2A domain, e.g. having an amino acid sequence according to SEQ ID NO: 21. The artificial CRE recognizes histone tails with specific methylated and/or acetylated sites. More preferably, the artificial CRE is selected from the group consisting of a micro antibody, a single chain antibody, an antibody fragment, an affibody, an affilin, an anticalin, an atrimer, a DARPin, a FN2 scaffold, a fynomer, and a Kunitz domain. The transposase is a PiggyBac transposase, a sleeping beauty transposase, or a Tol2 transposase. Preferably, the PiggyBac transposase is a wild-type PiggyBac transposase, a hyperactive PiggyBac transposase, a wild-type PiggyBac-like transposase, or a
hyperactive PiggyBac-like transposase.
The examples teaches construction of the transposase expression plasmids: KATA2A-PBw-TAF3, TAF3- PBw, PBw-TAF3, KAT2A-PBw, Taf3-haPB, haPB, KATA2A-haPB-TAF3, KATA2A-haPB and haPB-TAF3. The examples teaches generation and analysis of clone pools, as starter cell line the dihydrofolate reductase-deficient CHO cell line, CHO/DG44. The examples teach clone pools generated with the KAT2A-PBw, TAF3-PBw, PBw-TAF3 and KAT2A-PBw-TAF3 fusions variants and wt PiggyBac transposase antibody yields were determined at day 14 of the fed-batch process. The examples teach the effects of the different fusion domains on a hyperactive (ha) transposase. Clone pools derived from this transposase achieved a ~5.1-fold higher antibody concentration than the wt PiggyBac transposase pools. Compared to the hyperactive PiggyBac transposase pools antibody yields of the KAT2A-haPB, TAF3-haPB, haPB-TAF3 and KAT2A-haPB-TAF3 fusion variant clone pools were found to be ~2-fold, ~2.8-fold, ~2.4-fold and 2.9-fold higher. The examples teach transposase specific genomic integration of the transposons, the genomic integration of the transposons was analyzed by Real-Time qPCR.
The specification fails to provide a sufficient adequate written description demonstrating that they were in possession of the full scope of the invention at the time of the filling. The limitation “histone reader element” or “histone reader domain” encompasses an open-ended and undefined range of potential substitutions within the polypeptide, without any indication of the functional consequence or rationale for such substitutions. While the specification describes examples of a few variants, the phrase “histone reader element” or “histone reader domain”” covers an unlimited number of combinations and permutations beyond what is supported with the written disclosure. Furthermore, “histone reader element is selected from the group consisting of a micro antibody, a single chain antibody, an antibody fragment, an affibody, an affilin, an anticalin, an atrimer, a DARPin, a FN2 scaffold, a fynomer, and a Kunitz domain”; they are structural and functionally unrelated, and the specification does not provide any examples demonstrating that they were in possession of the full scope of the invention at the time of the filling .
The broad, open-ended nature of the claim is not commensurate with the limited and specific guidance provided in the specification.
As such, the claims encompasses significantly more than what is disclosed in the specification and does not satisfy the written description requirement under 35 U.S.C 112(a).
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claim 59.
The claims listed in the statement of rejection but not otherwise discussed are rejected because they are similarly not limited to particular polynucleotides that are considered to be adequately described by the specification.
Response to Amendments and Arguments on the Grounds of 35 U.S.C 112(a).
With respect to the claim 59 is rejected under Grounds of 35 U.S.C 112(a), Applicant's arguments filed 08/27/2025 have been fully considered but they are not persuasive.
The applicant response asserts “Although disagreeing with the Examiner, Applicant has amended claim 1 for the sake of prosecution efficiency: the claimed polypeptide is now defined as comprising "a transposase and at least one heterologous histone reader domain," with "the transposase" defined as "selected from the group consisting of a wild-type PiggyBac transposase, a hyperactive PiggyBac transposase, a wild-type PiggyBac-like transposase, and a hyperactive PiggyBac-like transposase" and "the at least one heterologous histone reader domain" defined as "a plant homeodomain (PHD) type zinc finger."
However, the Applicant did not amend the independent claim 59. The critical essential elements are the transposase and histone reader element; however, the claim is not limited to any particular transposase or histone reader element, the claim do not specify what type of transposase or histone reader element.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JULIO GOMEZ RODRIGUEZ whose telephone number is (571)270-0991. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at 5712722916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JULIO WASHINGTON GOMEZ RODRIGUEZ/Examiner, Art Unit 1637
/J. E. ANGELL, Ph.D./Primary Examiner, Art Unit 1637
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