The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 30, 2026 has been entered.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Claims 2, 14-19, 21, 27-28, 30 are canceled. Claims 1, 3-11, 22, 23 are withdrawn. Claims 12-13, 20, 24-26, 29 are under consideration.
Priority: This application is a 371 of PCT/IB2020/051983, filed March 6, 2020, which claims benefit of foreign application 10201902002S, filed March 6, 2019. A copy of the foreign priority document has been received in the instant application and is in the English language.
Objections and Rejections
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.
Claims 12-13, 20, 24-26, 29 are rejected under 35 U.S.C. 103 as being unpatentable over Too et al. (US 20150361449, cited as WO 2014070111 on IDS 09.03.21; previously cited) in view of Ferrin et al. (2017 Isolation, Culture, and Expansion of Mesenchymal Stem Cells. In: Crook, J., Ludwig, T. (eds) Stem Cell Banking. Methods in Molecular Biology, vol 1590. Humana Press, New York, NY, 14 pages; previously cited).
Too et al. disclose a method for transfecting MSCs (mesenchymal stem cells) comprising transfecting (or exposing) MSCs to a transfection reagent comprising PEIMAX and PMAXGFP or PMAXGFP-BMP2 complex; treating (or exposing) the MSCs to DOPE/CHEMS, Tubastatin A and/or TSA (Trichostatin A) in combination; incubating the MSCs for at least 24 hours in the PEIMAX, PMAXGFP or PMAXGFP-BMP2, DOPE/CHEMS, Tubastatin A and TSA mixture, before the culture media was replaced with fresh media (at least paragraphs 0066-0067, 0069, 0153-0154 example 15, Figs. 53, 54, 56; instant claims 12-13). Too et al. disclose the PEIMAX and PMAXGFP or PMAXGFP-BMP2 complex are added directly to the MSCs and do not teach centrifugation during exposing the MSCs to PEIMAX, PMAXGFP or PMAXGFP-BMP2, DOPE/CHEMS, Tubastatin A and TSA and incubation of the MSCs in the mixture for at least 24 hours and also do not teach that the transfection mixture is removed during addition of the DOPE/CHEMS, Tubastatin A and TSA (at least paragraphs 0066-0067, 0069, 0153-0154 example 15, Figs. 53, 54, 56; instant claims 12-13, 24). Since Too et al. disclose transfecting MSCs as noted above, Too et al. can be deemed to disclose that the MSCs are in a culture flask or container. Too et al. do not explicitly teach the culture flask of at least 175 cm2 surface area.
Ferrin et al. disclose culture of mesenchymal stem cells in culture flasks including T175 flasks, T25 flasks, 6-well plates (at least p. 178).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed method comprising a method for transfecting MSCs, comprising transfecting (or exposing) MSCs to a transfection reagent comprising PEIMAX and PMAXGFP or PMAXGFP-BMP2 complex; treating (or exposing) the MSCs to DOPE/CHEMS, Tubastatin A and/or TSA in combination, where the DOPE/CHEMS, Tubastatin A and/or TSA are added directly to the MSCs in culture without removing the transfection reagent; incubating the MSCs for at least 24 hours in the mixture, where the PEIMAX and PMAXGFP or PMAXGFP-BMP2 complex are added directly to the MSCs and there is no centrifugation during exposing the MSCs to PEIMAX, PMAXGFP or PMAXGFP-BMP2, DOPE/CHEMS, Tubastatin A and TSA and incubation of the MSCs in the mixture, and wherein the method is performed in a culture vessel of at least 175 cm2 area (instant claims 12-13, 24). The motivation to do so is given by the prior art. Too et al. disclose a method for transfecting MSCs comprising adding PEIMAX and PMAXGFP or PMAXGFP-BMP2 complex directly to the MSCs and do not teach centrifugation during exposing the MSCs to PEIMAX, PMAXGFP or PMAXGFP-BMP2, DOPE/CHEMS, Tubastatin A and TSA and incubation of the MSCs for at least 24 hours in the mixture. Ferrin et al. disclose culture vessels for MSC culture include T175 flasks. Therefore, one of ordinary skill would have reasonable motivation to incorporate the T175 flask disclosed in Ferrin et al. for the culture vessel in the method for transfecting MSCs without centrifugation of Too et al. One of ordinary skill would have a reasonable expectation of success because culture flasks having a 175 cm2 were available and known in the art for culturing cells.
Regarding the instant limitations “wherein a multipotent phenotype of the transfected MSCs is substantially unchanged by the transfection,” it is noted that since Too et al. disclose a method comprising transfecting MSCs with the same components recited and at the same conditions, it would follow that the transfected MSCs have a multipotent phenotype that is substantially unchanged by the transfection. Nevertheless, in example 15, Too et al. disclose continued expression of the transgene in the MSCs treated with DOPE/CHEMS, Tubastatin A and/or TSA (Trichostatin A) in combination (at least paragraph 0154), where this indicates potential efficient cell therapy with prolonged release of therapeutic product (at least paragraph 0154). Therefore, Too et al. can be deemed to disclose that the transfected MSCs have a multipotent phenotype that is substantially unchanged by the transfection.
Regarding instant claims 13, 24, Too et al. disclose transfecting MSCs with DNA/cationic polymer in addition with DOPE/CHEMS and a HDACi to the transfection mixture and incubation for at least 24 hours, before the culture media was replaced with fresh media (paragraphs 0066, 0067, 0069, Fig. 53, 54, 56), where there is no centrifugation step present during exposure and incubation of the MSCs in the transfection reagent and HDACi in combination.
Regarding instant claim 20, Too et al. disclose the MSCS are also capable of osteogenic differentiation (at least paragraphs 0153-0154).
Regarding instant claims 25-26, 29, Too et al. disclose co-administration of the DOPE/CHEMS, Tubastatin A and TSA to the MSCs transfected with PEIMAX and PMAXGFP or PMAXGFP-BMP2 complex (at least paragraphs 0066-0067, 0069, 0153-0154 example 15).
Reply: Applicants’ amendments/remarks have been considered but they are not persuasive. The reasons for maintaining the 103 rejection are the same as previously noted and are incorporated herein.
Regarding Applicants’ remarks that the instant method provides a particularly effective method of transfection, which allows scalability, i.e. by balancing transfection efficiency and stability and that the studies of the instant application describe the addition of polyplexes and TrafEn directly into culture vessels, without the need for centrifugation.
Applicants’ remarks are not persuasive. In this instance, Too et al. disclose the same transfection efficiency and stability for transfecting MSCs in a method for transfecting MSCs comprising adding directly into the MSCs in culture, a transfection reagent and DOPE/CHEMS, Tubastatin A and/or TSA (Trichostatin A) in combination, without a centrifugation step (example 15). Too et al. disclose the applications of TrafEn gene-drug combination in stem cell technologies with MSCs (example 15). In example 15, Too et al. disclose continued expression of the transgene in the MSCs treated with DOPE/CHEMS, Tubastatin A and/or TSA (Trichostatin A) in combination (at least paragraph 0154), where this indicates potential efficient cell therapy with prolonged release of therapeutic product (at least paragraph 0154).
Applicants assert that first, Too et al. do not teach or suggest incubating MSCs in the transfection mixture for a period of at least 24 hours, as required by the instant claims. Applicants assert that Figs. 53, 54, 56 (paragraphs 0066, 0067, 0069) are figure descriptions intended to help the reader better understand and not to teach a reproducible protocol. Applicants assert that viewed in this context, a person of skill in the art would understand that the figure descriptions would be interpreted in light of the disclosure’s operative methods section of Too et al., at paragraphs 0172 to 0201.
Applicants’ remarks are not persuasive. As previously noted, it is known that 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. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). MPEP 2123.
It is known that “[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). MPEP 2123.
In this instance, at Figs. 53, 54, 56 (paragraphs 0066, 0067, 0069), and example 15 (paragraph 0154), Too et al. disclose methods comprising transfecting MSCs comprising transfecting (or exposing) MSCs to a transfection reagent comprising PEIMAX and PMAXGFP or PMAXGFP-BMP2 complex; treating (or exposing) the MSCs to DOPE/CHEMS, Tubastatin A and/or TSA in combination; incubating the MSCs for at least 24 hours, where there is no teaching or disclosure that the methods performed to obtain the results in Figs. 53, 54, 56, comprise a centrifugation step during exposure and incubation of the MSCs in the transfection reagent, DOPE/CHEMS, Tubastatin A and/or TSA in combination. Even if paragraphs 0066, 0067, 0069 are figure descriptions for Figs. 53, 54, 56, the descriptions still expressly disclose method steps for transfecting MSCs comprising adding the reagents and components noted above and further would be interpreted with example 15 (paragraphs 0153-0154), which describe Figs. 53, 54, 56 and the method steps performed to obtain the results depicted in Figs. 53, 54, 56, where there is also no teaching or disclosure that the methods performed to obtain the results in Figs. 53, 54, 56, comprise a centrifugation step during exposure and incubation of the MSCs in the transfection reagent, DOPE/CHEMS, Tubastatin A and/or TSA in combination.
Applicants again assert that the office has misinterpreted the teachings of Too et al. in relation to the instant claims. Applicants assert that a person of ordinary skill would interpret the figure descriptions of Figs. 53, 54, 56 with paragraphs 0172 to 0201 of Too et al.
Applicants’ remarks are not persuasive. As previously noted, the cells being transfected in the methods section of paragraphs 0172-0201 are neuronal cells and not MSCs. Applicants’ remarks do not make any sense because it is not clear why one of ordinary skill would look to paragraphs 0172-0201, which disclose a method for transfecting neuronal cells, to interpret Figs. 53, 54, 56, which are disclosing the results of transfection of MSCs. In this instance, Figs. 53, 54, 56, at paragraphs 0066, 0067, 0069, and example 15 already disclose a method that successfully transfects MSCs with transfection reagent, DOPE/CHEMS, Tubastatin A and/or TSA in combination. Therefore, Applicants’ remarks that a person of ordinary skill would interpret the figure descriptions of Figs. 53, 54, 56 with paragraphs 0172 to 0201 of Too et al. are not found persuasive.
Applicants also assert that in paragraph 0177, Too et al. imply that the transfection procedure is not limited to just differentiated cells (i.e. neuronal cells) but may also include undifferentiated cells.
Applicants’ remarks are not persuasive. It is not clear where paragraph 0177 of Too et al. expressly disclose transfection for undifferentiated cells, including MSCs. Too et al. expressly disclose neuronal cell cultures (paragraph 0172) are the cells being transfected in paragraph 0177 (paragraphs 0172-0177).
As previously noted, in paragraph 0177 of the “Methods” section noted by Applicants, the cells being transfected are neuronal cells transfected with plasmid DNA expressing EGFP (paragraphs 0172-0177), which are completely different than the MSCs transfected with PEIMAX complexed PMAXGFP (control) or PMAXGFPBMP2 (human BMP2 cloned into PMAXGPF vector) in paragraph 0067.
At paragraph 0067 (Fig. 54), Too et al. expressly disclose that MSCs were transfected with PEIMAX complexed PMAXGFP (control) or PMAXGFPBMP2 (human BMP2 cloned into PMAXGPF vector) at N/P= 10 (BMP2). Post transfection, cells were treated with or without DOPE/CHEMS, 5 μM Tubastatin A, and 150 nM TSA in combination or individually. 24 hours post transfection, culture media was replaced with fresh media containing HDACi according.
Therefore, the MSCs were incubated in the transfection mixture (PEIXMAX complexed PMAXGFP or PMAXGFPBMP2) with DOPE/CHEMS (fusogenic lipid), 5 μM Tubastatin A (a HDACi), and 150 nM TSA (a HDACi) for at least 24 hours before the culture media was replaced with fresh media containing additional HDACi (paragraph 0067), and where there is no centrifugation step present during exposure and incubation of the MSCs in the transfection reagent, Tubastatin A and/or TSA in combination.
Therefore, Applicants’ remarks that in the experiments of paragraph 0067, the LPEI/pDNA complex and the cells were not incubated for 24 hours per paragraph 0177 are not persuasive. It is not clear how Applicants arrived at their interpretation that paragraph 0177 conveys that the LPEI/pDNA complex and the cells in paragraph 0067 were not incubated for 24 hours.
Applicants assert that in Too et al.’s cell viability assay, which tested the potential toxicity of LPEI/pDNA complexes to host cells, the transfection mixture was applied to cells for 15 minutes or 4 hours (Too et al. paragraph 0187). Applicants assert that the times selected were to explore toxicity associated with longer incubation times and were not used in the general transfection protocol. Applicants assert that regardless, the incubation periods used to examine toxicity are far removed from the incubation time required by the instant claims lasting at least 24 hours. Applicants assert that thus, at best, Too et al. teach incubating host cells (e.g. MSCs) with a transfection mixture comprising a nucleic acid construct complexed with cationic polymer for 5 minutes, 15 minutes, or 4 hours.
Applicants’ remarks are not persuasive. Paragraph 0187 of Too et al. describes cell viability of neuronal cells and is not being relied upon in the 103 rejection. Paragraph 0187 of Too et al. does not describe cell viability and/or toxicity of the MSCs transfected according to Figs. 53, 54, 56 (Too et al. paragraphs 0066, 0067, 0069) and in example 15 (paragraph 0154).
At Fig. 53 (paragraph 0066), Too et al. disclose MSCs were transfected with PEIMAX complexed with 1.5 μg of PMAXGFP at N/P=10 in the absence or presence of DOPE/CHEMS and/or HDACi (100 nM Trichostatin A). After 24 h of transfection, culture media were replaced with fresh media with or without Trichostatin A and further incubated for 48 h. (paragraph 0066). Therefore, the MSCs were incubated in the transfection mixture (PEIXMAX complexed PMAXGFP) with DOPE/CHEMS (fusogenic lipid) and 100 nM Trichostatin A (a HDACi) for at least 24 hours before the culture media was replaced with fresh media containing additional HDACi (paragraph 0066), and where there is no centrifugation step present during exposure and incubation of the MSCs in the transfection reagent and Trichostatin A in combination. Too et al. disclose that the addition of DOPE/CHEMS and TSA to the transfection mixture significantly enhanced transfection of MSCs (Fig. 53).
The teachings of Fig. 54 of Too et al. are noted above, which also disclose transfecting MSCs and that the MSCs are incubated in the transfection mixture (PEIXMAX complexed PMAXGFP or PMAXGFPBMP2) with DOPE/CHEMS (fusogenic lipid), 5 μM Tubastatin A (a HDACi), and 150 nM TSA (a HDACi) for at least 24 hours before the culture media is replaced with fresh media containing additional HDACi (paragraph 0067), and where there is no centrifugation step present during exposure and incubation of the MSCs in the transfection reagent, Tubastatin A and/or TSA in combination. Too et al. disclose that in Fig. 54, the expression levels of BMP2 in the presence or absence of DOPE/CHEMS and/or HDACi (TSA, Tubastatin A) in MSC were quantified using qPCR (paragraph 0154). Too et al. disclose that the combination of DOPE/CHEMS and TSA significantly increased BMP2 overexpression (~200,000 fold compared to control) and that the combination of DOPE/CHEMS and Tubastatin A also increased BMP2 overexpression compared to control (~80,000 fold) (Fig. 54).
At Fig. 56 (paragraph 0069), Too et al. show bright field images of MSCs from 3 up to 21 days post transfection. MSCs were transfected with PEIMAX mediated delivery of PMAXGFP or PMAXGFP-BMP2. After transfection, cells were treated with DOPE/CHEMS and 150 nM TSA individually or in combination. 72 hours post transfection, culture media was replaced with (A) expansion media alpha-MEM/10% FBS or (B) osteogenic differentiation media (alpha-MEM supplemented with 10% FBS, 10 mM β-glycerophosphate, 10 nM dexamethasone, and 0.2 mM ascorbic acid. Cells were then further incubated and the respective media was replaced every 3 days (paragraph 0069). Therefore, the MSCs were incubated in the transfection mixture (PEIXMAX complexed PMAXGFP or PMAXGFPBMP2) with DOPE/CHEMS (fusogenic lipid) and 150 nM TSA (a HDACi) for at least 24 hours (72 hours) before the culture media was replaced with fresh media (paragraph 0069), and where there is no centrifugation step present during exposure and incubation of the MSCs in the transfection reagent and TSA in combination.
Therefore, Applicants’ remarks that Too et al., at best, teach incubating host cells (e.g. MSCs) with a transfection mixture comprising a nucleic acid construct complexed with cationic polymer for 5 minutes, 15 minutes, or 4 hours are not persuasive.
As noted above, the methods of Fig. 53, 54, 56 disclose incubation of MSCs with a transfection mixture comprising a nucleic acid construct complexed with cationic polymer, and DOPE/CHEMS (fusogenic lipid), 5 μM Tubastatin A (a HDACi), and 150 nM TSA (a HDACi), for at least 24 hours, as recited in the instant claims, before replacement with fresh media.
Therefore, Applicants’ remarks that paragraphs 0066, 0067, 0069 of Too et al. relied upon by the office are silent to the details of how transfection is performed and when and how DOPE/CHEMS and HDACi are added are not found persuasive.
Applicants previously pointed to Figure 11 of Too et al. as leading one of ordinary skill in the art away from prolonged incubation times.
Applicants’ remarks are not persuasive. It is noted that Fig. 11 of Too et al. shows histograms visualizing that increasing N/P ratios reduced cell viability in neuronal cells (paragraph 0024) and is not being relied upon in the 103 rejection. Too et al. disclose that for transfection of MSCs, addition of DOPE/CHEMS and a HDACi to the transfection mixture comprising DNA/cationic polymer and incubation for at least 24 hours, significantly enhanced transfection of MSCs and increased BMP2 overexpression (paragraphs 0066, 0067, Fig. 53, 54).
Applicants assert that second, the instant method also excludes the use of centrifugation, which is touted by Too et al. as improving the transfection efficiency and cytotoxicity of the methods disclosed therein. Applicants assert see, e.g. example 1.
Applicants’ remarks are not persuasive. It is noted that example 1 is disclosing to establish an optimal protocol for transfection of neuronal cells, where mild centrifugation improved transfection efficiency and reduced cytotoxicity in neuronal cells (paragraph 0134). The 103 rejection is not relying on example 1 of Too et al. for the obviousness rejection. As noted above, Too et al. disclose that for transfection of MSCs, addition of DOPE/CHEMS and a HDACi to the transfection mixture comprising DNA/cationic polymer and incubation for at least 24 hours, significantly enhanced transfection of MSCs and increased BMP2 overexpression (paragraphs 0066, 0067, Fig. 53, 54), where there is no mention of a centrifugation step being present during exposure and incubation of the MSCs to the transfection reagent and HDACi in combination.
Applicants further point to Too et al.’s Figures 11, 12, and 14, considered together as to what they convey to one of ordinary skill in the art.
Applicants’ remarks are not persuasive. It is noted that Figures 11, 12, and 14 are disclosing transfection of neuronal cells (paragraphs 0024, 0025, 0027, example 1, example 3) and are not being relied upon in the 103 rejection. As noted above, Too et al. disclose that for transfection of MSCs, addition of DOPE/CHEMS and a HDACi to the transfection mixture comprising DNA/cationic polymer and incubation for at least 24 hours, significantly enhanced transfection of MSCs and increased BMP2 overexpression (paragraphs 0066, 0067, Fig. 53, 54), where there is no centrifugation step present during exposure and incubation of the MSCs in the transfection reagent and HDACi in combination.
Applicants assert that the office cites Ferrin et al. as curing the deficiencies of Too et al. by allegedly disclosing culture of MSCs in various size flasks. Applicants assert that the office has not established that the teachings of Ferrin et al. are relevant to transfection methods.
Applicants’ remarks are not persuasive. Ferrin et al. has disclosed that mesenchymal stems can be contained in culture flasks including T175 flasks, T25 flasks, 6-well plates (at least p. 178). As noted above, Too et al. has established that for transfection of MSCs, addition of DOPE/CHEMS and a HDACi to the transfection mixture comprising DNA/cationic polymer and incubation for at least 24 hours, significantly enhanced transfection of MSCs and increased BMP2 overexpression (paragraphs 0066, 0067, Fig. 53, 54), where there is no centrifugation step present during exposure and incubation of the MSCs in the transfection reagent and HDACi in combination. Therefore, Too et al. fairly disclose that the MSCs are in a culture flask or container. Therefore, it would be obvious that a culture flask, or container, as disclosed in Ferrin et al., while differing in size, would have the same function of containing the MSCs of Too et al. for cell culture experiments and techniques, including transfection.
Applicants assert that furthermore, the office has not established that Ferrin et al. teach or suggest any conditions for transfecting MSCs with DNA/polymer complexes, much less the particular combination of conditions recited in the instant claims.
Applicants’ remarks are not persuasive. The deficiency of Ferrin et al. to not teach transfecting MSCs with DNA/polymer complexes and the combination of conditions recited in the instant claims remedied by Too et al. As noted above, Too et al. disclose transfecting MSCs with DNA/cationic polymer in addition with DOPE/CHEMS and a HDACi to the transfection mixture and incubation for at least 24 hours, significantly enhanced transfection of MSCs and increased BMP2 overexpression (paragraphs 0066, 0067, Fig. 53, 54), where there is no centrifugation step present during exposure and incubation of the MSCs in the transfection reagent and HDACi in combination.
Applicants assert that the office’s reliance on MPEP 2123 is misplaced in the context of the instant rejection. Applicants assert that here, Too et al. do not merely disclose more than one alternative, the reference discourages use of prolonged incubation times and encourages use of centrifugation.
Applicants’ remarks are not persuasive. While Too et al. disclose mild centrifugation improved transfection efficiency and reduced cytotoxicity in neuronal cells (example 1), Too et al. do not discourage use of prolonged incubation times and encourage use of centrifugation for all cells. For MSCs at least, Too et al. disclose transfecting MSCs with DNA/cationic polymer in addition with DOPE/CHEMS and a HDACi to the transfection mixture and incubation for at least 24 hours, significantly enhanced transfection of MSCs and increased BMP2 overexpression (paragraphs 0066, 0067, Fig. 53, 54), where there is no centrifugation step present during exposure and incubation of the MSCs in the transfection reagent and HDACi in combination.
For at least these reasons, the 103 rejection is maintained.
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 12-13, 20, 24-26, 29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13, 15 of U.S. Patent No. 10100331 (‘331) in view of Too et al. (supra) in view of Ferrin et al. (supra). Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant claims and the ‘331 patent claims are drawn to a method for transfecting a stem cell comprising transfecting the stem cell with a genetic material; adding (or exposing) the cell to a first agent capable of redirecting endocytosed nucleic acids from intracellular acidic compartments (or the first agent comprises a lipid fusogenic agent or a peptide fusogenic agent) and a second agent capable of stabilizing a microtubular network of the stem cell. The ‘331 patent claims 1, 13 recite the cell is a stem cell, where it is disclosed in the ‘331 specification that a stem cell is a mesenchymal stem cell. Therefore, it would be obvious that the cell that is transfected in the ‘331 patent claims is selected from an MSC. The ‘331 patent claims also do not recite centrifugation during exposure of the MSCs to the transfection reagent and HDACi in combination. The ‘331 patent claims differ from the instant claims by not reciting the incubation period is at least 24 hours and a culture vessel having a surface area of at least 175 cm2. However, in view of the teachings of Too et al. and Ferrin noted above, it would have been obvious to incorporate an incubation of at least 24 hours in the ‘331 patent claims because Too et al. disclose transfecting MSCs with DNA/cationic polymer in addition with DOPE/CHEMS and a HDACi to the transfection mixture and incubation for at least 24 hours, significantly enhanced transfection of MSCs and increased protein (BMP2) overexpression (paragraphs 0066, 0067, Fig. 53, 54), where, like the ‘331 patent claims, there is no centrifugation step present during exposure and incubation of the MSCs in the transfection reagent and HDACi in combination, and incorporate the MSCs in culture flasks including T175 flasks as suggested in Ferrin et al. for performing the method in the ‘331 patent claims because a culture flask, or container, as disclosed in Ferrin et al., while differing in size, will have the same function of containing the MSCs of the ‘331 patent claims for cell culture experiments and techniques, including transfection. One of ordinary skill would have a reasonable expectation of success because culture flasks having a 175 cm2 were available and known in the art for culturing cells and transfection at longer incubation increases transfection efficiency of MSCs. Regarding the instant dependent claims, it would be obvious that the steps and/or features are reasonably present and would be obvious in the method of the ‘331 patent dependent claims and/or it would have been obvious to incorporate the elements and/or features not explicitly recited in the ‘331 patent dependent claims, in view of the teachings of Too et al. noted above, to thereby arrive at the instant claims.
Reply: Applicants’ amendments/remarks have been considered but they are not persuasive.
Applicants assert that instant claim 12 is directed to a method for transfecting MSCs with a nucleic acid construct from which one or more functional genes are expressed. Applicants assert that the method comprises incubating the MSCs in the transfection mixture for a period of at least 24 hours. Applicants assert that the MSCs are not centrifuged during exposure to the transfection mixture, to the first agent and a second agent, or during the incubating step. Applicants assert further that the method is performed in a culture vessel of at least 175 m2 surface area.
Applicants’ remarks are not persuasive. It is noted that the ‘331 patent claims already do not recite centrifuging the stem cells during exposure to the transfection mixture, to the first agent and second agent, during incubation, or any combination thereof. Therefore, it would be obvious that a centrifuging step is not present or required in the ‘331 patent claims.
As noted above, the ‘331 patent claims do differ from the instant claims by not reciting the incubation period is at least 24 hours and a culture vessel having a surface area of at least 175 cm2. However, the nonstatutory double patenting rejection over the ‘331 patent is made further in view of Too et al. and Ferrin et al. As noted above, the ‘331 patent claims 1, 13 recite the cell is a stem cell, where it is disclosed in the ‘331 specification that a stem cell is a mesenchymal stem cell. Therefore, it would be obvious that the cell that is transfected in the ‘331 patent claims is selected from an MSC. It would have been obvious to incorporate an incubation of at least 24 hours in the ‘331 patent claims because Too et al. disclose transfecting MSCs with DNA/cationic polymer in addition with DOPE/CHEMS and a HDACi to the transfection mixture and incubation for at least 24 hours, significantly enhanced transfection of MSCs and increased protein (BMP2) overexpression (paragraphs 0066, 0067, Fig. 53, 54), where like the ‘331 patent claims, there is no centrifugation step present during exposure and incubation of the MSCs in the transfection reagent and HDACi in combination, and incorporate the MSCs in culture flasks including T175 flasks as suggested in Ferrin et al. for performing the method in the ‘331 patent claims because a culture flask, or container, as disclosed in Ferrin et al., while differing in size, will have the same function of containing the MSCs of the ‘331 patent claims for cell culture experiments and techniques, including transfection. One of ordinary skill would have a reasonable expectation of success because culture flasks having a 175 cm2 were available and known in the art for culturing cells and transfection at longer incubation increases transfection efficiency of MSCs.
Applicants assert that Too et al. and Ferrin et al. do not cure the deficiencies of the ‘331 patent claims.
Applicants’ remarks are not persuasive. The reasons for maintaining Too et al. and Ferrin et al. are the same as noted above.
No claim is allowed.
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/Marsha Tsay/Primary Examiner, Art Unit 1656