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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 05/06/2026 has been entered.
Election/Restrictions & Status of Claims
Applicant’s election without traverse of Group III (claims 8-15 and 24-27) in the reply filed on 08/12/2024 was previously acknowledged.
With the cancellation of unelected claims 1-6 and claims 18-22, the withdrawal of unelected claims 7, 16-17, and 23 is made Final.
Applicants have cancelled claim 14 and added new claims 29-31. New claims are included in Group III.
Accordingly, claims 8-13, 15, 24-27, and 29-31 are under examination.
Response to Arguments
Applicant's arguments filed 05/06/2026 have been fully considered but they are not persuasive.
Applicants have cancelled claim 14; the 112a rejection of claim 14 is withdrawn.
Applicants have not amended or argued persuasively about the 103 rejections; the 103 rejections have been maintained. They are rewritten to address amendments. Further discussion of arguments are addressed at the end of this Office Action.
Any rejection or objection not reiterated herein has been overcome by amendment.
Maintained Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
The rejection below is a reiteration of the rejection of Claims 8-15 and 24-27 made in the Final Office Action dated 2/06/2026.
Claim 8 Interpretation: Claim 8 is drawn to a method of inhibiting or reducing the expression and/or activity of at least two master regulators selected from the group consisting of: ETV4, MLXIPL, MEOX2, DDN, PRKCB, and OTP, in a subject having a glioblastoma, wherein the inhibition or reduction is carried out by administering one or more agents to the subject, wherein the agent is a short hairpin RNA (shRNA) or silencing RNA (siRNA); i.e., the agent is not limited to a direct inhibitor of any one of the genes listed.
Claims 8 – 11, 15, and 25 – 27 remain rejected and claim 29 is newly rejected under 35 U.S.C. 103 as being unpatentable over Berezovsky (Berezovsky AD, et. al. Neoplasia. 2014 Mar;16(3):193-206, 206.e19-25), hereinafter Berezovsky in view of Farouz (WO-2010108126-A2), hereinafter Farouz which is cited on the IDS filed 08/12/2024, wherein claim 11 is evidenced by Fontanet (Fontanet PA, et. al. Cereb Cortex. 2018 Jan 1;28(1):236-249), hereinafter Fontanet, as discussed in the Final Office Action of 2/06/2026 and reiterated below.
Regarding reducing the expression and/or activity of MEOX2 and OTP of claims 8 – 10, 15, 25, and 27, Berezovsky teaches knockdown of Sox2 in glioblastoma derived cells using shRNA reduced the expression of MEOX2, OTP, and Protein kinase, cAMP-dependent, catalytic, β, the latter reads on instant PRKCB (page 203, left col. paragraph 1; Table W1). The reduction of such genes corelated with downregulated expression of genes associated with stem cells and malignancy (abstract). The glioblastoma derived cells are from a patient with glioblastoma (GBM) (abstract). Berezovsky’s method reads on instant method wherein the RNA interference agent is a short hairpin RNA (shRNA), as amended, and that reduces expression of at least two of the recited genes (MEOX2 and OTP; claim 8), at least three of the recited genes (MEOX2, OTP, and PRKCB; claim 10) (MEOX2 and PRKCB; claim 29) and one additional master regulator selected from the group consisting of: … PRKCB (claim 27), wherein the master regulator is MEOX2 (claim 9), the agent is shRNA (claims 15 and 25), as recited in instant application.
Regarding claim 26, Berezovsky teaches reduced tumorigenicity of xenograft glioblastomas deficient for Sox2 (generated using RNAi agents) relative to the control group (without Sox2 RNAi) in subjects (page 194, right col. paragraph 4; page 195, left col. paragraph 4; page 200, left col. paragraph 2; Figure 6A, B).
Berezovsky does not teach that the method comprises administering to a subject having glioblastoma (claim 8), or inhibit or reduce the expression and/or activity of ETV4 (claim 11), rather treating cells derived from a glioblastoma patient.
However, Farouz teaches a method comprising administering to a subject a composition comprising one or more repressors, wherein the one or more repressors modulates at least one component of a cellular pathway associated with the pluripotency of a cell (claim 59), wherein the at least one component is…Sox-2 (claim 62). Such subject is suffering from a number of diseases, one of which is glioblastoma (pg. 316, line 24). Farouz teaches two or more compositions of repressors can be administered at the same time (page 27, lines 23 – 27).
Regarding claim 11, Farouz further teaches the method comprises contacting a cell from an individual suffering from cancer in vivo with a composition comprising one or more repressors that inhibits or reduces the transcription, translation, and/or activity of MEOX2 (claim 8; page 4, line 21) and PEA3 (page 97, line 17), where PEA3 is another name for ETV4 as evidenced by Fontanet (page 237, left col. paragraph 2).
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have substituted glioblastoma derived cells with glioblastoma as the population to which an RNA interference agent is administered because Farouz teaches administering an agent that knocks down Sox2 to glioblastoma patients and Berezovsky also teaches administering an agent that knocks down Sox2 to glioblastoma derived cells, wherein the latter are from a patient with GBM. Further, Berezovsky also taught that such knockdown would have the downstream effect of knocking down MEOX2, OTP, and PRKCB, which corelate with reduction in malignancy. Therefore, one would be motivated to administer the agent in glioblastoma patient for the advantage of knocking down known master regulator genes such as the recited genes. The skilled artisan would have had a reasonable expectation of success that substituting glioblastoma derived cells to a subject with glioblastoma in the method of Berezovsky would also result in knocking down MEOX2 in cells of glioblastoma patients, and such method could be effective and work as predicted because Berezovsky 1) demonstrated knock down of MEOX2, OTP, and PRKCB in glioma-derived cells (as a result of inhibiting an upstream entity, by an RNAi agent); and 2) such knock-down corelates with decrease in malignancy. See MPEP 2143 I (B) and 2144 II.
Thus, Berezovsky in view of Farouz make obvious instant claims 8-11, 15, 25-27, and 29.
Claim 12 remains rejected and Claim 30 is newly rejected under 35 U.S.C. 103 as being unpatentable over Berezovsky (Berezovsky AD, et. al. Neoplasia. 2014 Mar;16(3):193-206, 206.e19-25), hereinafter Berezovsky in view of Farouz (WO-2010108126-A2), hereinafter Farouz which is cited on the IDS filed 08/12/2024, wherein claim 11 is evidenced by Fontanet (Fontanet PA, et. al. Cereb Cortex. 2018 Jan 1;28(1):236-249), hereinafter Fontanet (claim 11) as applied to claims 8 – 11, 15, 25 – 27 and 29 above and further in view of Chelban (Chelban V, et. al. 2017 Jun 1;100(6):969-977), hereinafter Chelban in view of Amberger (Amberger VR, et. al. Cancer Res. 1998 Jan 1;58(1):149-58), hereinafter Amberger, as discussed in the Final Office Action of 2/6/2026 and reiterated below.
Berezovsky in view of Farouz makes obvious claims 8 and 9 as set forth above. While Berezovsky teaches a method of reducing the expression and/or activity of MEOX2, OTP, and PRKCB, neither Berezovsky nor Farouz teach an inhibitor of NKX6-2. However, Farouz teaches glial progenitors transplanted into the brains of developing rats resulted in widespread myelin-producing cells (page 62, lines 31 – 33).
Chelban teaches NKX6-2 encodes a transcriptional repressor and deficiency of NKX6-2 results in hypomethylation in the brain (Abstract; page 976, left col. paragraph 1).
Amberger teaches gliomas are characterized by extensive infiltration of the surrounding normal brain tissue (page 149, left col. paragraph 1). Amberger teaches glioblastoma cells from patient tumors easily attach and spread on a CNS myelin substrate and direct correlation between the in vivo grade of malignancy of a given glioma and the ability to spread and migrate on a CNS myelin substrate (page 149, right col. paragraph 2; page 152, left col. paragraph 2). Amberger teaches future blockers of spreading on myelin may allow inhibition or significant slowing down the infiltration of white matter by malignant gliomas (page 157, right col. paragraph 3).
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Berezovsky and Farouz regarding repressors that inhibit or reduce the transcription, translation, and/or activity of MEOX2 and PRKCB in a subject with the teachings of Chelban regarding deficiency of NKX6-2 results in hypomethylation in the brain with the teachings of Amberger regarding glioblastoma cells from patient tumors easily attach and spread on a CNS myelin substrate to arrive at the claimed method wherein the master regulators are MEOX2 and PRKCB and further comprises an inhibitor of NKX6-2. One would have been motivated to combine the teachings of Berezovsky, Farouz, Chelban, and Amberger to treat glioblastoma as Amberger teaches gliomas are characterized by extensive infiltration of the surrounding normal brain tissue and future blockers of spreading on myelin may allow inhibition or significant slowing down the infiltration of white matter by malignant gliomas. One would have a reasonable expectation of success in combining the teachings as Farouz teaches two or more compositions of repressors can be administered at the same time and Chelban teaches deficiency of NKX6-2 results in hypomethylation in the brain.
Thus, Berezovsky and Farouz in view of Chelban and Amberger make obvious instant claims 12 and 30.
Claim 13 remains rejected under 35 U.S.C. 103 as being unpatentable over Berezovsky (Berezovsky AD, et. al. Neoplasia. 2014 Mar;16(3):193-206, 206.e19-25), hereinafter Berezovsky in view of Farouz (WO-2010108126-A2), hereinafter Farouz which is cited on the IDS filed 08/12/2024, wherein claim 11 is evidenced by Fontanet (Fontanet PA, et. al. Cereb Cortex. 2018 Jan 1;28(1):236-249), hereinafter Fontanet as applied to claim claims 8 – 11, 15, and 25 – 27 above, and further in view of Sunayama (Sunayama, J. et. al. Stem Cells, Volume 28, Issue 11, November 2010, Pages 1930–1939), hereinafter Sunayama in view of Sirek (Sirek AS, et. al. Endocrinology. 2009 Aug;150(8):3483-92), hereinafter Sirek in view of Dmitrenko (Dmitrenko, V.V. et al. Cytol. Genet. 48, 383–391 (2014)), hereinafter Dmitrenko in view of Kwei KA, et al (2012), PLoS ONE 7(9): e46518.), hereinafter Kwei, as discussed in the Final Office Action of 2/6/2026 and reiterated below.
Neither Berezovsky nor Farouz teach the remaining genes MLXIPL or DDN of claim 13. However, Sunayama teaches agents that inhibit the MEK/ERK signaling pathway reduce the expression of Sox2 in glioblastoma cells (page 1933, right col. paragraph 1; Figure 1C, F). Sunayama teaches the activity of the PI3K/AKT and ERK pathways are elevated in the vast majority of glioblastomas and that only a minority of patients responded to treatment using MEK inhibitors suggesting that single-agent treatment may be insufficient to control glioblastoma (page 1932, left col. paragraph 3; page 1939, left col. paragraph 2 – 3). Sunyama teaches combined PI3K and MEK/ERK inhibition could be effective in the treatment of human cancer (page 1939, right col. paragraph 2).
Regarding reducing the expression of MLXIPL of claim 13, Sirek teaches ChREBP is also known as MLX interacting protein like (MLXIPL) (page 3484, left col. paragraph 2). Sirek teaches a MEK inhibitor reduces ChREPB (MLXIPL) expression (page 3489, left col. paragraph 1; Figure 5H; page 3491, left col. paragraph 1).
Regarding DDN of claim 13, Dmitrenko teaches DDN is involved in the functioning of neural cells and involved in processes such as synaptic transmission and an expression level of DDN of more than twice in one group of glioblastomas relative to another group of glioblastomas (page 388, right col. paragraph 3).
Regarding reducing the expression and/or activity of DDN of claim 13, Kwei teaches dendrin (DDN) is a top gene that confers resistance to PI3K inhibitors in the treatment of cancers (page 2, left col. paragraph 2).
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Berezovsky regarding repressors that inhibit or reduce the transcription, translation, and/or activity of Sox-2 with the teachings of Sunayama regarding agents that inhibit the MEK/ERK signaling pathway reduce the expression of Sox2 in glioblastoma cells with the teachings of Sirek regarding a MEK inhibitor reduces ChREPB (MLXIPL) expression with the teachings of Dmitrenko regarding DDN expression is upregulated in glioblastomas with the teachings of Kwei regarding DDN is a potential resistor of PIK3 inhibitor activity to arrive at the claimed method where the one or more agents that inhibit or reduce the expression and/or activity of each of ETV4, MLXIPL, MEOX2, DDN, and OTP comprise shRNA targeting Sox2 and ETV4, MEK inhibitor, and wherein the method reduces the tumorigenicity of the glioblastoma in the subject. One would have been motivated to combine the teachings of Farouz, Berezovsky, Sunayama, Sirek, Dmitrenko, and of Kwei to treat glioblastoma as Sunayama teaches single-agent treatment may be insufficient to control glioblastoma and combinatorial targeted therapy is likely to prove more successful. One would have a reasonable expectation of success in combining the teachings as Berezovsky teaches activated signaling pathways up-regulate Sox2 in glioblastoma and reduced tumorigenicity of xenograft glioblastomas deficient for Sox2 using RNAi; Sunayama teaches MEK/ERK signaling pathway inhibitors reduce the expression of Sox2 in glioblastoma cells, and Kwei teaches that inhibiting DDN will potentiate the effect of PI3K inhibitors used in the treatment of cancers.
Thus, Berezovsky and Farouz in view of Sunayama, Sirek, Dmitrenko, and Kwei make obvious instant claim 13.
New Claim 31 is rejected under 35 U.S.C. 103 as being unpatentable over Berezovsky (Berezovsky AD, et. al. Neoplasia. 2014 Mar;16(3):193-206, 206.e19-25), hereinafter Berezovsky in view of Farouz (WO-2010108126-A2), hereinafter Farouz which is cited on the IDS filed 08/12/2024, wherein claim 11 is evidenced by Fontanet (Fontanet PA, et. al. Cereb Cortex. 2018 Jan 1;28(1):236-249), hereinafter Fontanet (claim 11) as applied to claims 8 – 11, 15, 25 – 27 and 29 above and further in view of Lee (US 10119144 B2).
Regarding claim 31, the method of claim 8 is discussed above. Neither Berezovsky nor Farouz teach that the method of claim 8 further comprises administering an inhibitor of ASCL1.
However, before the effective filing date of instant invention, Lee had taught a method comprising delivering to a cell a composition comprising an isolated single stranded oligonucleotide of 8 to 40 nucleotides in length having a region of complementarity that is complementary with at least 5 contiguous nucleotides of a number of genes that includes ASCL1 (claim 1; in vivo, claim 6), for the treatment of cancers such as glioma ([113], Table 2). The inhibitory nucleic acid is single stranded or double stranded such as siRNA [46] or shRNA (col. 11, 2nd para).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of instant invention to combine agents known to be capable of use in glioblastoma as taught by Berezovsky and Farouz together, and Lee to derive synergistic/additive benefits and also to reduce the dosage amount of the active ingredients. The MPEP in 2144.06 I states:
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
There would have been a reasonable expectation of success in making the combination because all the agents being combined target genes that are known to be upregulated in glioblastoma, and whose expression was already demonstrated at least individually, and in combination, the agents were expected to inhibit their expression as they would individually.
Thus, Berezovsky and Farouz in view of Lee make obvious instant claim 31.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
Response to Arguments
Applicant's arguments filed 05/06 with respect to a prima facie case of obviousness of claim rejections under 35 USC § 103 have been fully considered but they are not persuasive for the reasons discussed below.
Claims 1-11, 15, and 25-27, Berezovsky in view of Farouz
Applicants essentially assert that: (A) there is no teaching provided to one of skill in the art in the applied ref of Berezovsky because 1) Berezovsky does not teach that the genes in question are downregulated in cancer stem-like cells (CSC), 2) Berezovsky provides a long list of genes, and one would not be motivated to pick the genes in question from such a long list and 3) arguing that decreasing Sox2 expression could favor metaplastic sarcomatous by citing Berezovsky, "[t]hese findings have potential clinical implications in that any intervention aimed at decreasing Sox2 activity or downstream pathways in [gliosarcoma, a variant of GBM] could favor metaplastic sarcomatous tumor growth" (page 204); (B) one would not have a reasonable expectation of success in selecting one or two genes from the same long list of genes; (C) the use of impermissible hindsight to pick and choose the features of the methods of the claims and combine them from the references cited by the Examiner. Applicants further cite MPEP § 2142: impermissible hindsight must be avoided and the legal conclusion must be reached on the basis of the facts gleaned from the prior art.
The Remarks are not found persuasive. In response to (A), the teachings of Berezovsky, perhaps here, Applicant is arguing about claim 26, because none of the other claims are directed to treatment, they simply require administering to a glioblastoma subject. Further, with respect to treatment as required by claim 26, Berezovsky’s teachings have been considered as a whole. MPEP 2123 teaches:
Rejection Over Prior Art’s Broad Disclosure Instead of Preferred Embodiments
I. PATENTS ARE RELEVANT AS PRIOR ART FOR ALL THEY CONTAIN
"The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)).
In the instant case, all of Berezovsky’s findings, including those that are mentioned only once, are significant with respect to glioblastoma. This is evident in last line of Berezovsky’s abstract, “Our results indicate that Sox2 regulates the expression of key genes and pathways involved in GBM malignancy, in both cancer stemlike and differentiated cells, and maintains plasticity for bidirectional conversion between the two states, with significant clinical implications.”. Berezovsky teaches knockdown of Sox2 in glioblastoma cells using shRNA reduced the expression of MEOX2 and OTP (page 203, left col. paragraph 1; Table W1). Unlike what Applicants say the risk of sarcomatous development is limited to GS. See excerpt regarding GS from pg. 194:
PNG
media_image1.png
200
400
media_image1.png
Greyscale
i.e., Berezovsky warns about a ~2% variant of GBM called GS, which is currently not clinically distinguished from GBM (but should) has a different etiology than the majority of GBM. Berezovsky’s study warns against the downregulation of Sox2 in these variants. For the rest of GBM, Berezovsky shows that Sox2 knockdown in GBM SDCs abolished dedifferentiation and acquisition of CSC phenotype in vitro and decreased tumorigenicity (page 204, R col. paragraph 1. Therefore, even for claim 26, there is sufficient motivation to rely on the reference of Berezovsky.
With respect to (B) there is no expectation of success, this is not found persuasive. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). It is noted that the features upon which applicant relies (i.e., using an siRNA that directly inhibits or hybridizes to a gene(s) from a long list of genes) are not recited in the rejected claim(s). Rather the claim recites one or more agents; the genes applicant argue about, is a functional limitation. Once an agent is picked, in this case SOX2, changes in multiple gene expression will be seen. Applicants may consider amending the claims to recite direct inhibitors of the chosen genes. Applicants have not provided any reasoning as to why there would be no reasonable expectation of success in administering shRNA targeting SOX2, as the applied reference has, and meeting the functional limitations i.e., inhibiting expression/activity in a glioblastoma patient, which is the scope of claims 8 – 11, 15, 25, and 27 and new claims 29-31. Regarding claim 26, the scope of the claim encompasses a treatment; i.e., an in vivo effect. As discussed above, it is within the purview of the ordinary skilled artisan to see that extrapolation of Berezovsky’s method of treating glioblastoma derived cells to a glioblastoma patient, is reasonable. Berezovsky explicitly show: 1. that reducing Sox2 reduces tumorigenicity, for e.g., see results displayed in Fig.4; and 2. The correlation of MEOX2 with SOX2 knockdown has further basis in glioblastoma multiforme (Table W1 footnote). Further, the secondary reference of Farouz provides that missing clinical element that would result in a predictable method of administering to a patient, such predictable method will ensure a reasonable expectation of success.
With respect to (C), MPEP states,
"[a]ny judgment on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper." In re McLaughlin, 443 F.2d 1392, 1395, 170 USPQ 209, 212 (CCPA 1971).
In the instant case, the only facts that Examiner has used in the rejection are facts from the prior art and not instant disclosure.
Further, the Remarks state that the secondary references e.g., Farouz, etc., is also a long list of cancers, and there is no indication in Farouz that an agent knocking down Sox2 should be administered to a subject having glioblastoma.
This is not persuasive. The administration of an agent to a subject, generally would require particular procedures to be followed by research and clinical scientists, that extend beyond demonstration of gene knockdown in specific cell-lines and incorporate safety, efficacy and ethical considerations. Farouz provide the assurance that a gene may be inhibited in glioblastoma patients. Such assurance can be gleaned from Farouz despite the limited mention of glioblastoma.
Claim 12, Berezovsky in view of Farouz, Chelban, and Amberger
Applicants argue that the references alone or together, do not teach a method comprising administering to a subject having a glioblastoma.
This is not persuasive. As discussed supra, Farouz provides the missing clinical link.
Claim 13, Berezovsky in view of Farouz, Sunayama, Sirek, Dmitrenko, and Kwei
Applicants argue that one of skill would have to make several logical leaps to arrive at a method of administering one or more agents to inhibit or reduce the expression and/or activity of each of ETV4, MLXIPL, MEOX2, DDN, and OTP to a subject having a glioblastoma.
Further, as for 1. Above; i.e., there is (A) no motivation to combine the two references to arrive at the particular combination of the claimed invention; and (B) one would not have a reasonable expectation of success in practicing the claimed invention based on the cited references.
This is not persuasive. 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).
Claims 8 and 24, Berezovsky in view of Hugnot
Applicants amended claims to remove Nkx2.2.
Thus, this rejection is withdrawn.
Applicants arguments are not dispositive, the rejection is maintained.
Conclusion
No claims allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHABANA MEYERING, Ph.D. whose telephone number is (703)756-4603. The examiner can normally be reached M - F: 9am to 5pm 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, Ram Shukla can be reached on (571) 272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SHABANA S MEYERING/Examiner, Art Unit 1635
/CATHERINE KONOPKA/Primary Examiner, Art Unit 1635
