DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendments
Applicant's amendments filed 11/14/2024 to claims 25, 28, and 29 have been entered. Claims 1-4, 6-12, 14-20, and 25-29 are pending, of which claims 1-4, 6-9, 12, 14, 15, and 25-29 are under consideration on the merits. Claims 10, 11, and 16-20 remain withdrawn from consideration. References not included with this Office action can be found in a prior action.
The instant amendments to claim 29 have overcome the alternate anticipation and obviousness rejections of record over Luxenhofer, which are withdrawn. New grounds of rejection are set forth below necessitated by said amendments.
Any other rejections of record not particularly addressed below are withdrawn in light of the claim amendments and/or applicant’s comments.
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4, 6-9, 12, 14, 15, and 25-29 are rejected under 35 U.S.C. 103 as being unpatentable over Oberbek et al. (Biotechnol Bioeng. (epub. Oct. 2010), 108, 600-610).in view of Luxenhofer et al. (Journal of Controlled Release (2011), 153, 73-82) and Erlach et al. (Biomaterials (2011); 32, 5291-5303).
This rejection addresses the embodiment of 2-methyl-oxazoline (MeOx) or 2-ethyl-oxazoline (EtOx) for claims 1, 25, and 29.
Oberbek teaches methods of lentiviral vector-mediated gene transfer in CHO cells in suspension culture or HEK cells in suspension culture by utilizing a (cationic) polyethyleneimine polymer (Abstract; detailed methods on p601-603), reading on claims 1, 6, 8, 9, 25, and 29, both embodiments of cells for claim 25, and the product-by-process limitations to turbulent agitation of claim 28. Oberbek teaches a serum-free culture medium when culturing the CHO cells and a culture medium comprising 10% serum when culturing the HEK cells (see the Abstract and p601, subheading “Cell Culture”), reading on claims 2 and 3 and the embodiment of ProCHO5 as a chemically defined medium for claim 4, and the embodiment of no serum for claim 25. Oberbek teaches that the infected HEK and CHO cells are both capable of producing lentiviral particles (p602, subheading “Production and Titering of LV stocks), reading on claims 7 and 26, and the embodiment of a viral vector and viral particles for the pharmaceutically active ingredient of claim 15. Oberbek teaches transfecting CHO cells with a pDNA comprising eGFP (Fig.1 and subheading “Plasmids” on p601-602), which is used as a selection marker for the isolation of stably and high-producing cell lines which are then further transfected with a protein of interest for subsequent protein production (p601, paragraph starting “Here, a method…” ), reading on plasmid DNA (pDNA) claim 27.
Regarding claim 1, 25, and 29, Oberbek does not teach the embodiment of either 2-methyl-oxazoline (MeOx) or 2-ethyl-oxazoline (EtOx). Regarding claim 12, Oberbek does not teach the cell culture composition comprises 0.01 to 15 wt. %, water- soluble poly(oxazoline) in relation to the total weight of the cell culture. Regarding claim 14, Oberbek does not teach that the water-soluble poly(oxazoline) has at least 90 wt% based on the total weight of the water-soluble poly(oxazoline), of repeat structural units of formula I, wherein R” means methyl or ethyl.in the culture media or cells capable of suspension culture.
Luxenhofer teaches a composition comprising 2-methyl-oxazoline (MeOx) or 2-ethyl-oxazoline (EtOx) homopolymers contacted with plated/adherent MCF-7 cells contacted with a composition culture media lacking serum and assaying the cells for cytotoxicity or cellular uptake of the oxazoline compounds (p74-75, subheading 2.3 and 2.4; see Table 1, H1-H4 for oxazoline homopolymers), reading on claims 1, 14, and 25.Luxenhofer teaches that MDF-7 cells are viable when contacted with the oxazoline polymers at specific concentrations in the range of 0.01-1% by weight (Fig. 4I, noting H1-H4 as EtOx as set forth in Table 1), reading on the concentration range of claim 12. Luxenhofer teaches that polyoxazoline polymers would be useful in micellar drug delivery (to cells) (“Conclusion” on p81), reading in-part on claims 1 and 25. Luxenhofer teaches that polyoxazoline polymers would be advantageous as an alternative to polyethylene glycol (PEG) polymers for the cellular delivery enzymes and drugs and POx polymers are chemically well-defined, non-toxic, exhibit low immunogenicity and are small enough to be easily excreted from the body (p73, paragraph starting “POx are attractive…” through paragraph ending “…from the body.” on p74). Luxenhofer teaches that 2-ethyl-oxazoline (EtOx) is capable of entering the mammalian cells (p77, paragraph starting “Finally, H3*…”), reading on claim 1.
Erlach teaches methods of delivering DNA to mammalian cells comprising contacting said cells with a copolymer comprising a poly(2-methyl-2-oxazoline) monomer (Abstract; subheadings 2.3-2.6 on p5293-94 for detailed methods), reading in-part on claims 1, 25, and 29. Erlach teaches that positively charged polymers are typically to deliver therapeutic genes to cells in combination with polyethylene glycol (PEG) as PEG ameliorates the known cytotoxic effect of the positively charged polymers (paragraph spanning both columns on p5291). Erlach teaches PEG is prone to oxidative degradation in aqueous solutions and that poly(2-methyl-2 oxazoline) is structurally similar to PEG and would be a desirable alternative as poly(2-methyl-2 oxazoline) has a peptide-like structure that is resistant to autooxidation (paragraph spanning p5291-92), reading on claims 1, 25, and 29.
Regarding claims 1, 14, 25, and 29 and concentration range of claim 12, it would have been obvious before the invention was filed to substitute the 2-methyl-2-oxazoline (MeOx) or 2-ethyl-2-oxazoline (EtOx) of Luxenhofer at the concentration range of Luxenhofer for the polyethyleneimine cationic polymer of Oberbek in view of Erlach. A person of ordinary skill in the art would have had a reasonable expectation of success in doing so because both Luxenhofer and Oberbek are in part directed towards serum-free culture media compositions and associated methods of culturing mammalian cells, and because both Luxenhofer and Erlach teaches that there is a need in this art to find alternative bioinert polymers for gene delivery which would be satisfied by the poly(2-methyl-2-oxazoline) of Luxenhofer and likely the poly(2-ethyl-2-oxazoline) Luxenhofer given the high degree of structural similarity between these homopolymers and the teachings of Luxenhofer that poly(2-ethyl-2-oxazoline) is cell-permeant. The skilled artisan would have been motivated to do so because Luxenhofer teaches that polyoxazoline polymers would be useful to enhance cellular drug delivery (e.g. DNA delivery, as a species of drug or agent to be delivered to the cells) and Erlach teaches that copolymers comprising a polyoxazoline monomer would be useful as a cationic polymer to deliver DNA to mammalian cells, and so the addition would likely enhance delivery of the lentiviral vectors of Oberbek into the CHO cells of Oberbek in view of Erlach.
Regarding claim 27, It would have been obvious to a person of ordinary skill in the art before the invention was filed to further add the eGFP plasmid of Oberbek to the cell culture composition of Luxenhofer. A person of ordinary skill in the art would have had a reasonable expectation of success in doing so because both Luxenhofer and Oberbek are in part directed towards serum-free culture media compositions and associated methods of culturing mammalian cells. The skilled artisan would have been motivated to do so because Oberbek teaches that the addition would be predictably advantageous to because eGFP would then as a selection marker for the isolation of stably high-producing cell lines which can then be further transfected with a protein of interest for subsequent protein production.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the invention was filed.
Response to Arguments
Applicant's arguments on pages 7-12 of the reply have been fully considered, but not found persuasive of error for the reasons given below.
On pages 7-9 of the reply, Applicant alleges Oberbek is deficient by not teaching every element of claims 1, 25, and 29. Applicant appears to make similar arguments regarding Luxenhofer and Erlach on page 9 of the reply. This is not found persuasive of error because Oberbek is not applied alone, but in combination with Luxenhofer and Erlach, and the claimed invention becomes obvious when the references are considered together as a whole rather than each alone. Applicant’s allegation of error over the alleged nonpreferred embodiment of Oberbek directed towards DNA transfection of cells with PEI is not found persuasive, as A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. See M.P.E.P. § 2123.
On pages 10-11 of the reply, Applicant appears to traverse the motivation to combine Luxenhofer and Erlach with Oberbek. In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Applicant appears to be alleging there would be no motivation to pick poly(2-methyl-2-oxazoline) from the list of about 15 copolymers taught by Erlach. This is not persuasive because ALL of the copolymers of Erlach comprise poly(2-methyl-2-oxazoline) as set forth in Table 2 and only differ in molecular weight and grafting densities (i.e. “g”), and the claims were not otherwise amended in the instant reply to exclude the embodiment comprising poly(2-methyl-2-oxazoline),
As a final point and in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). None of Applicant’s arguments appear to address the specific rationale of record to arrive at a prima facie case for obviousness nor what the combination of references would or would not suggest to a person of ordinary skill in the art.
Conclusion
No claims are allowed. No claims are free of the art.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN C BARRON whose telephone number is (571)270-5111. The examiner can normally be reached 7:00am-3:30pm EDT/EST (M-F).
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/Sean C. Barron/Primary Examiner, Art Unit 1653
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