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 .
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-9 and 11-13, and trastuzumab in the reply filed on 8 December 2025 is acknowledged. The traversal is on the ground(s) that the only purpose of screening host cells using the claimed expression vectors would be via a protein expression method, which is not materially different than the claimed method. This is not found persuasive because the presence of the claimed expression vectors within a host cell could be determined via the use of PCR to detect the presence of the claimed expression vectors within a host cell without the need for a method of protein expression.
The requirement is still deemed proper and is therefore made FINAL.
Claims 10 and 14-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 8 December 2025.
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 1-15 are preceded by the word "Figure" instead of the abbreviation "FIG.".
37 CFR 1.84 (u)(1) states “Partial views intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter.”
In the current case, the view numbers for the partial views for Figure 15 that appear on several sheets are followed by "Cont." instead of a capital letter such as FIG. 1A, FIG. 1B, etc.
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.
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 - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. The file size must be listed in bytes. See item 1) a) or 1) b) above.
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 of the following informalities:
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on pg. 46 and 51-52. 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.
Appropriate correction is required.
Claim Rejections - 35 USC § 103
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 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.
Claim(s) 1, 3, 5-9, and 18-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hadlaczky (US Patent No. 8,389,802 B2) in view of Kim (Nucleic acids research 46.13 (2018): 6712-6725).
Regarding claim 1, Hadlaczky is drawn towards an invention concerned methods for preparing cell lines that contain artificial chromosomes and targeted insertion of heterologous DNA into the chromosomes (Col 2, lines 60-66). Hadlaczky teaches the use of homology targeting vectors (i.e.,. an expression vectors) that can incorporate heterologous genes (i.e., DNA fragments) into mammalian artificial chromosomes (i.e., into a region of open chromatin in mammalian cells) (Col 83, lines 44-60). Hadlaczky teaches that the homology targeting vectors may comprise a selectable marker (Col 83, lines 53-58), selected from puromycin (Col 83, lines 66-67). Hadlaczky teaches that the homology targeting vectors can both target a region of an artificial chromosome of interest and induce large scale amplification (i.e., the vectors include a targeting and amplification sequence) (Col. 82, lines 36-64). Hadlaczky teaches that the homology targeting vectors can encode a therapeutic gene of interest, including a cystic fibrosis transmembrane conductance regulator, that can be incorporated into the mammalian artificial chromosome (Col 83, lines 62-66). Hadlaczky teaches that preferred targeting sequences include mammalian ribosomal RNA (i.e., rRNA) gene sequences (i.e., rDNA) which target the heterologous DNA to integrate into the rDNA region of those chromosomes that contain rDNA (Col 5, lines 35-38).
Hadlaczky does not teach or suggest that the targeting and amplification sequence comprises the claimed SEQ ID NO: 1 (Claim 1).
However, one of ordinary skill in the art would have considered the teachings of Kim as both references are common fields of endeavor pertaining to the study of rDNA.
Kim is drawn towards a study concerned with variations in human chromosome 21 rRNA genes characterized by TAR (i.e. transformation-assisted recombination) cloning (Abstract). Kim teaches the use of an rDNA sequence from a CDC27 pseudogene , termed “JH2”, that comprises an rDNA sequence having 100% identity to the claimed SEQ ID NO: 1 (pg. 6718; see attached sequence alignment). Kim teaches that a library of bacterial artificial chromosomes and yeast artificial chromosomes were able to be generated that contain the CDC27 pseudogene JH2 comprising the claimed SEQ ID NO: 1 (pg. 6718-6719; see Figure 1).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the rDNA targeting sequence of Hadlaczky for an rDNA sequence comprising a sequence having 100% identity to the claimed SEQ ID NO: 1, as described by Kim. A person of ordinary skill in the art would have been motivated to do so in order to utilize a known pseudogene sequence that can be utilized to generate an artificial chromosome via the targeting of an rDNA region of the chromosome through the use of an rDNA sequence. A person of ordinary skill in the art would have had a reasonable expectation of success because Hadlaczky teaches that targeting sequences may include rDNA sequences while Kim teaches that the claimed SEQ ID NO: 1 was present within a known rDNA sequence that could be integrated into an artificial chromosome.
Regarding claim 3, Hadlaczky teaches that the homology targeting vectors can encode a therapeutic gene of interest, including a cystic fibrosis transmembrane conductance regulator (i.e., a single protein) (Col 83, lines 62-66).
Regarding claim 7, Hadlaczky teaches that exemplary host cells include CHO cells (Col 35, lines 5-25).
Regarding claim 8, Hadlaczky teaches that thymidine kinase deficient murine L cells (i.e., mouse cells) may be used as a host for the artificial chromosome (Col 70, lines 36-49).
Regarding claim 9, Hadlaczky teaches that exemplary host cells include HEK 293 cells (i.e., human cells) (Col 35, lines 5-25).
Regarding claim 18, Hadlaczky teaches that exemplary host cells include CHO cells (i.e., mammalian cells) (Col 35, lines 5-25). Hadlaczky teaches that the homology targeting vectors can encode a therapeutic gene of interest, including a cystic fibrosis transmembrane conductance regulator, that can be incorporated into the mammalian artificial chromosome (i.e., the DNA fragment encoding a therapeutic protein can be integrated into the host cell’s open chromatin of the artificial chromosome) (Col 83, lines 62-66).
Regarding claim 5, Hadlaczky teaches that multiple copies of a heterologous gene can be integrated into the artificial chromosome in order to generate a megachromosome comprising 6 amplicons (i.e., 6 copies of a nucleic acid sequence encoding a protein of interest) (Col 13, lines 9-14, Col 52, lines 15-28; see Figure 3).
Regarding claim 6, Hadlaczky teaches that exemplary host cells include HEK 293 cells (i.e., human cells) (Col 35, lines 5-25).
Regarding claims 19-20, Hadlaczky teaches that the homology targeting vectors can encode a therapeutic gene of interest, including a cystic fibrosis transmembrane conductance regulator (i.e., a single protein), that can be incorporated into the mammalian artificial chromosome (Col 83, lines 62-66).
Claim Rejections - 35 USC § 103
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 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.
Claim(s) 4, 11, and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hadlaczky (US Patent No. 8,389,802 B2) in view of Kim (Nucleic acids research 46.13 (2018): 6712-6725) as applied to claims 1, 3, 5-9, and 18-20 above, and further in view of Blanco (Acta Pharmaceutica (2019)).
Regarding claims 4, 11, and 13, the teachings of Hadlaczky in view of Kim are discussed above as applied to claims 1, 3, 5-9, and 18-20.
Hadlaczky in view of Kim does not teach or suggest that the protein of interest is trastuzumab (Claims 4, 11, and 13).
However, one of ordinary skill in the art would have considered the teachings of Blanco as both references are common fields of endeavor pertaining to the use of nucleic acids encoding antibodies.
Blanco is drawn towards a study concerned with the binding properties and activity of a novel therapeutic monoclonal antibody (Abstract). Blanco teaches that trastuzumab is a monoclonal antibody that is directed against HER2: a growth factor receptor that is overexpressed in invasive breast adenocarcinomas (pg. 28). Blanco teaches the use of a DNA plasmid encoding trastuzumab that was able to be expressed in target cells of interest (pg. 28).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the nucleic acid encoding an antibody of interest, as described by Hadlaczky in view of Kim, for a nucleic acid encoding trastuzumab, as described by Blanco. A person of ordinary skill in the art would have been motivated to do so in order to produce a therapeutic antibody that is directed against a receptor that is overexpressed in cancerous cells. A person of ordinary skill in the art would have had a reasonable expectation of success because both Blanco and Hadlaczky in view of Kim teach the use of nucleic acids encoding therapeutic antibodies.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KYLE T REGA whose telephone number is (571)272-2073. The examiner can normally be reached M-R 8:30-4:30, every other F 8:30-4:30 (EDT/EST).
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, 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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KYLE T REGA/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636