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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 06/08/2026 has been entered.
Status of Claims
Claims 1, 6, 9-11, 15-16, 20-21, 23, 25 and 30-31 are pending and examined on the merits herein.
Claims 1 and 25 are currently amended.
Claim 24 is currently cancelled.
Status of Rejections
The rejection of claims 1, 6, 9-11, 15-16, and 23 under 35 U.S.C. 103 as being unpatentable over Van Gaal (Journal of Controlled Release, 2011, 154: 218-232), in view of Fenton (Agnew. Chem., 2018, 57(41): 13582-13586; cited in IDS filed 08/24/2022), Youn (Expert Opinion on Biological Therapy, 2015, 15(9): 1337-3148), ThermoFisher (“Factors Influencing Transfection Efficiency,” retrieved from the Internet 11/21/2019 by Wayback Machine), and Morozov (Molecular Biology, 2012), 46(3): 391-406) is withdrawn in light of the amendment to claim 1 to incorporate the subject matter of cancelled claim 24.
The rejection of claims 1, 20-21 and 31 35 U.S.C. 103 as being unpatentable over Van Gaal (Journal of Controlled Release, 2011, 154: 218-232), in view of Fenton (Agnew. Chem., 2018, 57(41): 13582-13586; cited in IDS filed 08/24/2022), Youn (Expert Opinion on Biological Therapy, 2015, 15(9): 1337-3148), ThermoFisher (“Factors Influencing Transfection Efficiency,” retrieved from the Internet 11/21/2019 by Wayback Machine), Morozov (Molecular Biology, 2012), 46(3): 391-406), and Riss (Assay and Drug Development Technologies, 2004, 2(1): 51-62) is withdrawn in light of the amendment to claim 1 to incorporate the subject matter of cancelled claim 24.
The rejection of claims 1, 6, and 30 under 35 U.S.C. 103 as being unpatentable over Van Gaal (Journal of Controlled Release, 2011, 154: 218-232), in view of Fenton (Agnew. Chem., 2018, 57(41): 13582-13586; cited in IDS filed 08/24/2022), Youn (Expert Opinion on Biological Therapy, 2015, 15(9): 1337-3148), ThermoFisher (“Factors Influencing Transfection Efficiency,” retrieved from the Internet 11/21/2019 by Wayback Machine), Morozov (Molecular Biology, 2012), 46(3): 391-406), and Dong (PNAS, 2014, 111(11): 3955-3960), as evidenced by ThermoFisher-2 (“Useful Numbers for Cell Culture,” retrieved from the Internet) is withdrawn in light of the amendment to claim 1 to incorporate the subject matter of cancelled claim 24.
The rejection of claims 1 and 25 under 35 U.S.C. 103 as being unpatentable over Van Gaal (Journal of Controlled Release, 2011, 154: 218-232), in view of Fenton (Agnew. Chem., 2018, 57(41): 13582-13586; cited in IDS filed 08/24/2022), Youn (Expert Opinion on Biological Therapy, 2015, 15(9): 1337-3148), ThermoFisher (“Factors Influencing Transfection Efficiency,” retrieved from the Internet 11/21/2019 by Wayback Machine), Morozov (Molecular Biology, 2012), 46(3): 391-406), and Villeneuve (Environmental Toxicology and Chemistry, 2000, 19(11): 2835-2843) is maintained. Applicant’s arguments are addressed following the rejection.
The cancellation of claim 24 renders any rejections thereof moot.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1 and 25 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.
Claim 1 recites the limitation "the EC50" in the second line of step (v). There is insufficient antecedent basis for this limitation in the claim.
Claim 25 recites the limitation " the reference standard EC50" in line 2. There is insufficient antecedent basis for this limitation in the claim.
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.
Claims 1, 6, 9-11, 15-16, 23, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Van Gaal (Journal of Controlled Release, 2011, 154: 218-232), in view of Fenton (Agnew. Chem., 2018, 57(41): 13582-13586; cited in IDS filed 08/24/2022), Youn (Expert Opinion on Biological Therapy, 2015, 15(9): 1337-3148), ThermoFisher (“Factors Influencing Transfection Efficiency,” retrieved from the Internet 11/21/2019 by Wayback Machine), Morozov (Molecular Biology, 2012), 46(3): 391-406), and Villeneuve (Environmental Toxicology and Chemistry, 2000, 19(11): 2835-2843).
Regarding claim 1: Van Gaal teaches an in vitro method for screening non-viral gene delivery candidates for transfection efficiency (reads on potency), wherein the method comprises reading out transgene expression levels relative to a reference formulation after transfection (Abstract, Section 7.3, Section 8). Van Gaal teaches that the plasmid used for transfection comprises a reporter gene driven by a viral promoter (Section 2.1). Van Gaal further teaches that the delivery vehicle used in the method may be a lipid nanoparticle (Sections 4.1, 7.2). Val Gaal teaches seeding HepG2 cells on a cell culture plate (Section 5.1; Fig 2 caption) (step (i)), then transfecting the cells with a test or reference sample of the composition (Sections 6.1-6.2) (steps (ii), (iii)). Val Gaal teaches that the readout of transgene expression may be a direct detection of the proteins, or an indirect method based on enzymatic conversion of an added substrate to a colored or fluorescent product (Section 7.1), and may be determined by flow cytometry or microscopic analysis (Section 7.1). Van Gaal further teaches that expression levels are calculated relative to control values from the reference sample (Section 7.3) (step (iv)).
Val Gaal does not teach 1) carrying out the method with mRNA encapsulated in a lipid nanoparticle (LNP), 2) seeding a population of Hep-G2 cells on a cell culture plate comprising wells coated with collagen or lysine, 3) contacting the transfected cells with a first antibody specific for the polypeptide encoded by the mRNA and subsequently with a second, labeled antibody which is specific for the first antibody and detecting the second, labeled antibody, or 4) generating a dose response curve for the test sample and the reference sample and determining the EC50 of the test sample and reference sample.
Regarding difference 1: Val Gaal teaches carrying out the method disclosed therein with plasmid DNA. Val Gaal does not teaches carrying out the method with mRNA encapsulated in a lipid nanoparticle.
Fenton teaches transfecting HeLa cells with LNPs containing mRNAs (Abstract; p 13584, col 1, para 2).
Youn teaches that mRNA has major advantages to plasmid DNA for use in therapy (p 1345, col 1, para 2). Among other things, the use of mRNA reduces risk of insertion mutagenesis, eliminates the reliance on a promoter for modulating gene expression, allows for effective delivery of genetic cargo into non-dividing cells, and reduces vector-induced immunogenicity (p 1345, col 1, para 2).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Van Gaal to deliver mRNA instead of plasmid DNA in the LNPs, as taught by Fenton. One of ordinary skill in the art would have been motivated to make this modification because Youn teaches that mRNA has major advantages to plasmid DNA for use in transfection therapy. One of ordinary skill in the art would have had a reasonable expectation of reasonably making this modification because Fenton teaches that mRNAs can be encapsulated in LNPs, which can then be used to transfect cells in vitro.
Regarding difference 2: Val Gaal does not teach seeding a population of Hep-G2 cells on a cell culture plate comprising wells coated with collagen or lysine.
ThermoFisher teaches that some cell lines may need special coating materials, including collagen and poly-lysine, to attach to the culture plate and get the optimal transfection results (p 3, Media, para 3).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Van Gaal by using a cell culture plate wherein the wells are coated with collagen or lysine, as taught by ThermoFisher. One of ordinary skill in the art would have been motivated to make this modification because ThermoFisher teaches that collagen and lysing coating can help certain cell lines attach to the culture plate to get optimal transfection results. One of ordinary skill in the art would have had a reasonable expectation of reasonably making this modification because ThermoFisher teaches that plates comprising wells coated with collagen or lysine can be used as cell adhesion substrates for transfection experiments.
Regarding difference 3: Val Gaal does not teach contacting the transfected cells with a first antibody specific for the polypeptide encoded by the mRNA and subsequently with a second, labeled antibody which is specific for the first antibody and detecting the second, labeled antibody.
Morozov teaches transfecting HEK 239T cells with a vector encoding recombinant AFP (Abstract) using TransIT-LT1, a lipid-based transfection reagent (p 394, col 1, para 1), then performing immunofluorescence on the transfected cells (p 394, col 2, para 3). Morozov teaches treating the cells with an anti-AFP rabbit antibody (reads on first antibody), followed by Texas Red-labeled anti-rabbit IgG goat antibody (reads on second antibody), then imaging the cells using a fluorescent microscope (p 394, col 2, para 3).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Van Gaal by contacting the transfected cells with a first antibody specific for the polypeptide encoded by the mRNA and subsequently with a second, labeled antibody which is specific for the first antibody and detecting the second, labeled antibody, as taught by Morozov. One of ordinary skill in the art would have been motivated to make this modification to detect the amount of expression of the polypeptide encoded by the mRNA in the transfected cells. One of ordinary skill in the art would have had a reasonable expectation of reasonably making this modification because the method of Van Gaal comprises transfecting cells in vitro using an LNP, and Morozov teaches that immunofluorescence can be performed on cells transfected in vitro using an LNP.
Regarding difference 4: Val Gaal does not teach generating a dose response curve for the test sample and the reference sample and determining the EC50 of the test sample and reference sample (claim 1), and calculating the relative potency as a percentage of the reference standard EC50 (claim 25).
Villeneuve teaches that relative potency estimates are widely used to characterize and compare the potency of a wide variety of samples analyzed using in vitro bioassays (Abstract). Villeneuve teaches that relative potency is generally calculated by first determining the dose-response curves for the sample and standard (claim 1), then calculating the EC50 of a standard divided by the EC50 of a sample (claim 25) (Abstract).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Van Gaal by generating a dose response curve for the test sample and reference sample and determining the EC50 of each, as taught by Villeneuve. One of ordinary skill in the art would have been motivated to make this modification because Villeneuve teaches that relative potency estimates can be used to characterize and compare the potency of samples in in vitro assays. One of ordinary skill in the art would have had a reasonable expectation of reasonably making this modification because the method of Van Gaal is an in vitro assay.
Therefore, the method of claim 1 is rendered obvious over Van Gaal, in view of Fenton, Youn, ThermoFisher, Mozorov, and Villeneuve.
Regarding claims 9-11, 15-16 and 23: Following the discussion of claim 1, the transfection method taught in Val Gaal does not comprise the addition of ApoE during transfection (claim 9). Van Gaal teaches that the lipid nanoparticle may be a cationic lipid (Sections 3.1, 3.3, 7.2) (claim 10). Val Gaal teaches that the transfection studies are performed in adherent monolayer cell culture systems (Section 5.1; claim 15), wherein the cells are seeded into 96-well plates (Fig 2 caption; claim 11) 24 hours prior to transfection (Section 6.1; claim 16) and grown to reach 50-95% confluency on the day of transfection (Section 6.2; claim 15).
Van Gaal teaches that transfection time varies, ranging from 1h to continuous exposure until the time of analysis, but that in general, expression increases steeply with increasing incubation times up to around 4 h (claim 23), after which expression levels may either reach a plateau, continue to increase less steeply, or decrease, depending on the type and dose of complexes and cell type used (Section 6.4). Val Gaal teaches that the transfection takes place at 37℃ with 5% CO2 (Supplementary Materials p 5, para 2; claim 23).
Regarding claim 6: Van Gaal does not teach adding ApoE to the transfection medium.
Fenton teaches transfecting HeLa cells with mRNA LNPs in the presence of additional ApoE than is endogenously present in media (p 13584, col 1, para 2).
It would have been prima facie obvious to a person of ordinary skill the art before the effective filing date of the claimed invention to have modified the method of Van Gaal by adding ApoE to the transfection medium, as taught in Fenton. One of ordinary skill in the art would have been motivated to make this modification because Fenton teaches that the presence of ApoE increased the total amount of protein expression by approximately 140% (p 13584, col 2, para 2). One of ordinary skill in the art would have had a reasonable expectation of successfully making this modification because Fenton teaches that ApoE can be added to media during transfection.
Claims 1, 20-21 and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Van Gaal (Journal of Controlled Release, 2011, 154: 218-232), in view of Fenton (Agnew. Chem., 2018, 57(41): 13582-13586; cited in IDS filed 08/24/2022), Youn (Expert Opinion on Biological Therapy, 2015, 15(9): 1337-3148), ThermoFisher (“Factors Influencing Transfection Efficiency,” retrieved from the Internet 11/21/2019 by Wayback Machine), Morozov (Molecular Biology, 2012), 46(3): 391-406), Villeneuve (Environmental Toxicology and Chemistry, 2000, 19(11): 2835-2843), and Riss (Assay and Drug Development Technologies, 2004, 2(1): 51-62).
Van Gaal, in view of Fenton, Youn, ThermoFisher, Morozov, and Villeneuve render obvious claim 1.
Regarding claims 20-21 and 31: Val Gaal teaches seeding HeLa CCL-2 cells at a density of 12,000 cells per 96-well (Supplementary Materials p 2, para 1).
Val Gaal does not teach a specific seeding density for HepG2 cells in a 96-well. Specifically, Van Gaal does not teach seeding each well of a 96-well plate at a density of 15,000 cells per well to 35,000 cells per well (claim 20), seeding each well of the culture plate with 20,000 cells per well to 30,000 cells per well (claim 21), or seeding each well of the culture plate with 30,000 cells per well (claim 31).
Riss teaches seeding HepG2 cells at a density of 25,000 cells per well in a 96-well plate to establish an in vitro system for determining the time- and dose-dependent toxic effects of tamoxifen on HepG2 cells using cell viability, cytotoxicity, and apoptosis assays (Abstract; Fig 1-5). Riss further teaches seeding HepG2 cells at a density of 1,000, 10,000, or 35,000 cells per well in a 96-well plate to determine whether cell density affects in vitro tamoxifen potency (p 57, col 2, para 2 – p 58, col 1, para 1; Fig 6). Riss teaches that cell density in the assay plates affects the outcome of a screening assay, and therefore, cell density should be tightly controlled across experiments (p 60, col 1, para 2). Riss further teaches that cell density is a parameter that is easily controlled using standard operating procedures (p 60, col 1, para 2).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Van Gaal, in view of Fenton, Youn, ThermoFisher, and Morozov, by using a fixed cell density, such as 25,000 or 35,000 HepG2 cells per well in a 96-well plate, as taught in Riss. One of ordinary skill in the art would have been motivated to make this modification because Riss teaches that cell density should be tightly controlled across experiments, and that HepG2 cells seeded at a density of 25,000 or 35,000 cells per well in a 96-well plate can be used in an in vitro assay. One of ordinary skill in the art would have had a reasonable expectation of successfully making this modification because Riss teaches that HepG2 cells seeded at a density of 25,000 or 35,000 cells per well in a 96-well plate can be used in an in vitro assay.
Regarding claims 20-21: In the case where the claimed ranges overlap or lie inside ranges disclosed by the prior art, a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding claim 30: A prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. See MPEP 2144.05(I), In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Claims 1, 6, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Van Gaal (Journal of Controlled Release, 2011, 154: 218-232), in view of Fenton (Agnew. Chem., 2018, 57(41): 13582-13586; cited in IDS filed 08/24/2022), Youn (Expert Opinion on Biological Therapy, 2015, 15(9): 1337-3148), ThermoFisher (“Factors Influencing Transfection Efficiency,” retrieved from the Internet 11/21/2019 by Wayback Machine), Morozov (Molecular Biology, 2012), 46(3): 391-406), Villeneuve (Environmental Toxicology and Chemistry, 2000, 19(11): 2835-2843), and Dong (PNAS, 2014, 111(11): 3955-3960), as evidenced by ThermoFisher-2 (“Useful Numbers for Cell Culture,” retrieved from the Internet).
Van Gaal, in view of Fenton, Youn, ThermoFisher, Morozov, and Villeneuve render obvious claims 1 and 6.
Regarding claim 30: Van Gaal, in view of Fenton, Youn, ThermoFisher, and Morozov, does not teach the method of claim 6, wherein 4 μg/mL of ApoE is added. Specifically, Fenton, which teaches the addition of ApoE to culture medium, does not specify the concentration of ApoE used.
Dong, which is cited in Fenton (reference 6c), teaches lipopeptide nanoparticles for selective siRNA delivery (Abstract, Title). Dong teaches the use of 1 µg of ApoE per well in a 96-well plate (Supplementary Materials p 3, para 2). ThermoFisher-2 shows that each well of a 96-well plate holds approximately 0.1 to 0.2 mL of medium. Therefore, the concentration of ApoE taught in Dong is approximately 1 µg/0.1 mL to 1 µg/0.2 mL, or 10 µg/mL to 5 µg/ mL. In the case where the claimed ranges overlap or lie inside ranges disclosed by the prior art, a prima facie case of obviousness exists. See MPEP 2144.05(I).
Response to Arguments
Applicant's arguments and amendments dated 06/08/2026 have been fully considered but are moot in part and not persuasive in part due to the new grounds of rejection necessitated by applicant's amendments. To the extent that the arguments are pertinent to the current grounds of rejection they are responded to below.
Applicant argues: The Office Action’s assertion that Applicant's arguments rely on features not recited in the claims and are not commensurate in scope with the claimed invention (See Office Action p. 10 is incorrect, and this characterization overlooks the structure and requirements of the claimed method.
Claim 1 requires, inter alia, seeding HepG2 cells on wells coated with collagen or lysine, transfecting the cells with test and reference samples, detecting protein expression using a primary antibody followed by a labeled secondary antibody, and comparing expression levels to
determine relative in vitro potency.
Example 3 of the instant application provides direct experimental evidence demonstrating that the expressly claimed requirement of seeding HepG2 cells on collagen- or lysine-coated wells, as recited in claim 1, produces unexpected and material improvements in the performance of the claimed relative potency assay. Example 3 directly corresponds to these limitations and demonstrates that collagen-coated wells enable HepG2 cells to form a uniform monolayer rather than clumping, maintain cell attachment throughout the immunodetection process, and provide improved sensitivity and reproducibility in downstream quantitative measurements including dose-response curves and EC50 determination. Accordingly, the advantages described by Applicant are grounded in expressly recited claim features and do not rely on unclaimed subject matter.
In response: Applicant’s arguments are not persuasive.
First, the limitations recited by Applicant are taught in the prior art, as set forth in the rejection above.
Second, Example 3 of the specification does NOT provide experimental evidence demonstrating unexpected results arising from seeding HepG2 cells on collagen- or lysine-coated wells. The first paragraph of Example 3 (p 20, para 1) recites:
“The use of coated versus un-coated cell culture plates was also evaluated. Specifically,
collagen coated plates and poly-L-lysine coated plates were also evaluated. Collagen coated
plates allow the HepG2 cells to spread out and form a monolayer rather than balling up or clumping in cell culture treated plates. A monolayer formation of cells is essential for uptake
kinetics and improves sensitivity and precision of the assay.”
However, the experimental evidence in Example 3 is limited to the comparison of seeding density (Fig 5) and transfection time (Fig 6) on collagen-coated plates and poly-L-lysine coated plates (Fig 7). There is no data comparing the use of coated plates vs. uncoated plates.
Furthermore, there is no evidence presented in the specification that the use of uncoated plates results in “balling up or clumping.” Moreover, Example 2 of the specification demonstrates that HepG2 cells plated on uncoated plates are able to form a monolayer of cells (p 18, para 2).
Therefore, Example 3 does not amount to a demonstration of unexpected results arising from the use of coated plates.
Applicant argues: Claim 1 recites a specific, multi-step assay framework that includes controlled seeding conditions using coated wells, transfection of test and reference samples, and immunodetection based quantification of protein expression to determine the relative potency. Example 3 demonstrates that, in the absence of the claimed coating, HepG2 cells tend to clump or detach under assay conditions, particularly during handling associated with antibody-based detection. This leads to inconsistent or degraded signal and undermines the ability to generate reliable dose response curves. In contrast, when collagen-coated wells are used as required by claim 1, the cells form a stable and uniform monolayer, remain attached throughout the immunodetection procedure, and generate consistent signals that support accurate dose-response curve generation and EC50 determination. These results establish that the claimed coating condition is integral to achieving reliable determination of relative in vitro potency as required by claim 1 and its dependent claims. Moreover, these results are not predictable from general teachings related to improved cell attachment. Rather, they demonstrate an unexpected and application-specific effect of surface coating on LNP uptake kinetics and the quantitative accuracy of a potency assay
as required by the claims. The evidence is therefore fully commensurate with the scope of the
claimed invention.
In response: Applicant’s arguments are not persuasive. The argument regarding Example 3 has been addressed above. It is emphasized that Example 3 does NOT demonstrate “that, in the absence of the claimed coating, HepG2 cells tend to clump or detach under assay conditions, particularly during handling associated with antibody-based detection,” as asserted by Applicant.
Applicant argues: The cited references generally teach that surface coatings may improve cell attachment. However, such teachings do not address the specific assay context recited in the present claims. The references do not teach or suggest that HepG2 cells exhibit clumping or non-uniform growth
that adversely affects LNP-mediated tranifection or protein expression measurements. Nor does it recognize that antibody-based detection methods inherently involve processing conditions that may lead to cell detachment and variability in signal. Importantly, the cited references do not suggest that the use of collagen- or lysine-coated wells would improve quantitative assay outputs such as dose-response curve quality, EC50 determination, or relative potency calculations.
None of the cited references recognize the underlying technical problems addressed by Applicant, including variability in cell morphology affecting uptake kinetics, loss of cells during immunodetection procedures, complications specific to LNP-mediated transfection and distortion of quantitative outputs required for potency determination. In the absence of recognition of these problems, a person of ordinary skill in the art would have had no reason to select the claimed coating conditions for the purpose of improving potency assay performance for LNPs. The rejection therefore relies on impermissible hindsight reconstruction.
In response: Applicant’s arguments are not persuasive.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). As set forth in the rejection above, Van Gaal teaches an in vitro method for screening non-viral gene delivery candidates for transfection potency, wherein the method comprises reading out transgene expression levels relative to a reference formulation after transfection, and ThermoFisher teaches the use of collagen- or lysine-coating to improve adhesion to obtain optimal transfection results, thereby providing motivation to use collagen-or lysine-coated wells. In response to applicant’s argument that a person of ordinary skill in the art would have had no reason to select the claimed coating conditions for the purpose of improving potency assay performance for LNPs, the reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323, 76 USPQ2d 1662, 1685 (Fed. Cir. 2005); In re Lintner, 458 F.2d 1013, 173 USPQ 560 (CCPA 1972); In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990), cert. denied, 500 U.S. 904 (1991), discussed in MPEP 2144(IV).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Risa Takenaka whose telephone number is (571)272-0149. The examiner can normally be reached M-F, 12-7 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, Peter Paras can be reached at (571) 272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/RISA TAKENAKA/ Examiner, Art Unit 1632
/KARA D JOHNSON/ Primary Examiner, Art Unit 1632
Prosecution Insights