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 amendment filed on 02/26/2026 has been entered.
Claims 1-13, 16-17 and 19-20 are pending in the present application, and they are examined on the merits herein.
Response to Amendment
The rejection under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for New Matter was withdrawn in view of currently amended claims 16-17.
Claim Rejections - 35 USC § 112 (Lack of Written Description)
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.
Amended claims 16-17 are 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 is a new ground of rejection necessitated by Applicant’s amendment.
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc). Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” Vas-Cath Inc. v. Mahurkar, 19USPQ2d at 1117. The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed. ”Vas-Cath Inc. v. Mahurkar, 19USPQ2d at 1116.
The instant claims encompass a stable producer cell line, the stable producer cell line generated by: transfecting a packaging cell line selected from the group consisting of a GPRG packaging cell line, a GPRGT packaging cell line, and a GPRT-G packaging cell line with a concatemeric array comprising: (i) any first DNA fragments of any size obtained from a recombinant plasmid, wherein the recombinant plasmid is derived from pUC57-TL20c; and (ii) any second DNA fragments of any size obtained from a bleomycin antibiotic resistance cassette; wherein a molar ratio of the first DNA fragments to the second DNA fragments ranges from about 25:1 to about 1:25; and a lentiviral vector prepared from the stable producer cell line.
Apart from disclosing a concatermeric array comprising: (i) first DNA fragments obtained from a recombinant plasmid, wherein the recombinant plasmid is derived from pUC57-TL20c; and (ii) second DNA fragments obtained from a bleomycin antibiotic resistance cassette plasmid, wherein a molar ratio of the first DNA fragments to the second DNA fragments ranges from about 25:1 to about 1:25, wherein each of the first DNA fragments comprises a lentivirus cassette for a lentiviral transfer vector and wherein each of the second DNA fragments comprises a bleomycin antibiotic resistance cassette (see at least paragraphs [0015], [0023]-[0024],[0029]-[0030], [0076]-[0078], [0080], [0106]; Figs. 11-12 and 14), the instant specification fails to provide sufficient description for any other concatemeric array for transfecting a recited packaging cell line to produce a stable producer cell line that produces a lentiviral vector as claimed broadly, particularly a concatemeric array comprising any first DNA fragments of any size as long as they are obtained from a recombinant plasmid that is derived from pUC57-TL20c, and any second DNA fragments of any size as long as they are obtained from a bleomycin antibiotic resistance cassette. For example, apart from a first DNA fragment comprising a lentivirus cassette for a lentiviral transfer vector which essential element(s) and/or critical components do the other first DNA fragments possess so that the transfected producer cell line can produce a lentiviral vector? Additionally, apart from a second DNA fragment comprising a bleomycin antibiotic resistance cassette which essential element(s) and/or critical components do the other second DNA fragments possess such that a stable producer cell line can be generated to produce a lentiviral vector?
Since the prior art before the effective filing date of the present application (05/12/2016) did not provide sufficient written description and/or any guidance regarding the issues discussed above as evidenced at least by the teachings of Throm et al (Blood 113:5104-5110, 2009; IDS), Lee et al (Biotechnology and Bioengineering 109:1551-1560, 2012; IDS) and Wielogosz et al (Methods & Clinical Development 2:14063; doi:10.1038/mtm.2014.63, 12 pages, 2015; IDS); it is incumbent upon the present application to do so. The instant specification also fails to provide at least a sufficient number of a representative number of species for a broad genus of a stable producer cell line and a lentiviral vector prepared by the same stable producer cell line as claimed broadly.
The claimed invention as a whole is not adequately described if the claims require essential or critical elements which are not adequately described in the specification and which are not conventional in the art as of Applicants’ filing date. Possession may be shown by actual reduction to practice, clear depiction of the invention in a detailed drawing, or by describing the invention with sufficient relevant identifying characteristics such that a person skilled in the art would recognize that the inventor had possession of the claimed invention. Pfaff v. Wells Electronics, Inc., 48 USPQ2d 1641, 1646 (1998). The skilled artisan cannot envision the detailed structure at least of a representative number of species for a broad genus of a stable producer cell line and a lentiviral vector prepared by the same stable producer cell line as claimed broadly, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method. Adequate written description requires more than a mere statement that it is part of the invention and reference to a method of isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991). One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481, 1483.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
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.
Amended claims 16-17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. This is a new ground of rejection necessitated by Applicant’s amendment.
Claim 16 is vague and indefinite because of the term “derived from pUC57-TL20c”. It is unclear the nature and number of steps required to obtain a recombinant plasmid from which first DNA fragments are obtained. The term implies a number of different steps that may or may not result in a change in the functional characteristics of a recombinant plasmid from the pUC57-TL20c source. Moreover, there is no definition of the term “derived from” in the present application. Clarification is requested because the metes and bounds of the claim are not clearly determined.
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.
Amended claims 16-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Throm et al (Blood 113:5104-5110, 2009; IDS). This is a new ground of rejection necessitated by Applicant’s amendment.
The instant claims encompass a stable producer cell line, the stable producer cell line generated by: transfecting a packaging cell line selected from the group consisting of a GPRG packaging cell line, a GPRGT packaging cell line, and a GPRT-G packaging cell line with a concatemeric array comprising: (i) first DNA fragments obtained from a recombinant plasmid, wherein the recombinant plasmid is derived from pUC57-TL20c; and (ii) second DNA fragments obtained from a bleomycin antibiotic resistance cassette; wherein a molar ratio of the first DNA fragments to the second DNA fragments ranges from about 25:1 to about 1:25; and a lentiviral vector prepared from the stable producer cell line.
Throm et al already taught to generate a concatemeric array by excising the 2 DNA expression cassettes, the TL20 expression cassette for a lentiviral vector genome and the PGK-ble expression cassette for bleomycin, from their plasmid backbones; and ligating them in vitro at a 25:1 molar ratio, respectively, before transfecting these DNAs into GPRG cells (see at least section titled “Concatemer array transfection for stable SIN vector producer cell construction” at page 5106; and Figure 1-3). Throm et al further disclosed to select the transfected GPRG cells with drug, and isolating clones by limiting dilution, and demonstrated that concatemer-transfected clones yielded significant higher titers than did plasmid-transfected clones (right column, first paragraph at page 5106; and Figure 3). Throm et al also stated “After expanding our highest titer clone, designated GPRG-TL20-GFP, and freezing cells in liquid nitrogen, this line could be reliable thawed, propagated, and induced to yield 107 TU/mL. Induced titers remained above 107 TU/mL for 3 months of continuous passage (data not shown)” (right column, bottom of first paragraph at page 5106). Please note that the excised TL20 expression cassette is a fragment of a recombinant plasmid containing the TL20 expression cassette, which recombinant plasmid can be considered as a derivative of or being derived from pUC57-TL20c. Accordingly, the teachings of Throm et al meet all limitations of a stable producer cell line and a lentiviral vector prepared from the same producer cell line as claimed.
Therefore, the reference anticipates the instant claims.
Conclusion
Claims 1-13 and 19-20 are allowable.
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 Quang Nguyen, Ph.D., at (571) 272-0776.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s SPE, James Douglas (Doug) Schultz, Ph.D., may be reached at (571) 272-0763.
To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to Group Art Unit 1631; Central Fax No. (571) 273-8300.
Any inquiry of a general nature or relating to the status of this application or proceeding should be directed to (571) 272-0547.
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/QUANG NGUYEN/Primary Examiner, Art Unit 1631
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