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 .
Election/Restrictions & Status of Claims
Applicant’s election without traverse of Group III (claims 8 – 15 and 24 – 26) 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.
Accordingly, claims 8 – 15 and 24 – 27 are under examination.
Response to Arguments
Applicant's arguments filed 12/12/2025 have been fully considered but they are not persuasive.
Applicants amendments have overcome the 112a rejection of claims 8 – 13 and 24 – 27; the rejection of these claims is withdrawn. Applicants have not suitably amended or argued about the rejection of claim 14. The 112a rejection of claim 14 is maintained.
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.
Drawings
The drawings were received on 12/12/2025. These drawings are acceptable.
Specification
The amendment to abstract filed on 12/12/2025 is acknowledged.
Maintained Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
The rejection below is rewritten to limit the rejection made in the Non-Final Office Action dated 9/12/2025 to the rejection of Claim 14 only and addresses the amendment.
Claim 14 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Scope of the Invention
In the case of claim14, the genera are:
peptides derived from a master regulator to be used along with an RNA interference agent. The phrase derived from is being given the BRI based off the plain English dictionary meaning:
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Claim 14 depends from claim 8. Claim 8 is drawn to a method of inhibiting or reducing the expression and/or activity of at least one master regulator selected from the group consisting of: ETV4, MLXIPL, MEOX2, DDN, 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 at least one of the one or more agents is an RNA interference agent.
Claim 14 recites that the method further comprises administering a composition comprising a formulation of one or more peptides derived from at least one master regulator, one or more nanoparticles containing peptides derived from at least one master regulator, one or more dendritic cells containing peptides derived from at least one master regulator, RNA encoding at least one master regulator, one or more nanoparticles containing RNA encoding at least one master regulator, or one or more dendritic cells containing RNA encoding at least one master regulator.
Thus the claim in its broadest sense, requires that cells in which the gene whose expression was knocked down, be readministered the gene product by means of a composition derived from that gene product (peptide).
However, there is no written description on obtaining such a product.
In a narrower sense, a derived peptide is sufficiently small to function as an immunogenic peptide, but not be able to function to the fullest extent of the protein it is derived from.
Disclosure of a Complete or Partial structure – not described
Regarding peptides derived from a master regulator, the instant specification fails to disclose how derivation is to be achieved, or how a similar method was practiced in the art for a different agent or to provide even a single working example, prophetic or actual, of the claimed method that requires derivation of a peptide from a master regulator.
The only pertinent disclosure that provides some description is found at pages 12 – 14:
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The specification provides no written description as to the extent of derivation. Of course, one of ordinary skill in the art can synthesize a vector comprising the gene for an immunogenic peptide and expressing the gene product, and this would result in a derived peptide. However, the description of the specification does not allow one of ordinary skill in the art to determine that administering the gene product will not negate inhibiting or reducing expression or activity of any master regulator, as claimed and required by the independent claim.
Even if applicant was in possession of a vector expressing the peptide derived from a master regulator as of the filing date sought, the written description requirement is not met because the specification does not adequately describe the claimed invention.
As such, the breadth of the claimed method is enormously broad with an unfathomable number of structurally divergent and diverse peptides derived from at least one master regulator, wherein not even one has been tested to aid in the method as recited in the claim it depends from.
Accordingly, Applicant has not shown possession of the claimed invention at the time of effective filing.
Conclusion of written description
Therefore, the examiner concludes there is insufficient written description support for the instantly claimed genus of components to perform the claimed method. Specifically, there is no support for a peptide derived from a master regulator. Therefore, claim 14 is rejected for no description of deriving a peptide from a master regulator that will support the independent claim 8.
“Every patent must describe an invention. It is part of the quid pro quo of a patent; one describes an invention, and, if the law's other requirements are met, one obtains a patent.” (emphasis added). See Araid Pharmaceuticals Inc. v. Eli Lilly & Co. 593 F3d 1336, 94 USPQ2d 1161 (Fed. Cir. 2010).
“Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed… Application of the
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requirement, however, is not subsumed by the “possession” inquiry. A showing of “possession” is ancillary to the statutory mandate that “[t]he specification shall contain a written description
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of the invention,” and that requirement is not met if, despite a showing of possession, the specification does not adequately describe the claimed invention.” (emphasis added). See Enzo Biochem Inc. v. Gen-Probe Inc. 323 F3d 956, 63 USPQ2d 1609 (Fed. Cir. 2002).
Examiner Suggestion: Delete derived from and replace it with phrases for which there is support in the disclosure.
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 Non-Final Office Action dated 9/12/2025.
Claim 8 Interpretation: Claim 8 is drawn to a method of inhibiting or reducing the expression and/or activity of at least one master regulator selected from the group consisting of: ETV4, MLXIPL, MEOX2, DDN, 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).
Claims 8 – 11, 15, and 25 – 27 remain 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 Non-Final Office Action of 9/12/2025 and reiterated below.
Regarding reducing the expression and/or activity of MEOX2 and OTP of claims 8 – 11, 15, 25, and 27, Berezovsky teaches knockdown of Sox2 in glioblastoma derived cells using shRNA reduced the expression of MEOX2 and OTP (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 two of the recited genes (claim 8 and 27), wherein the master regulator is MEOX2 (claim 9), the agent is shRNA (claims 15 and 25), as recited in instant application. The remaining genes recited in claims 8 and 9 have not been considered because they have been recited as optional (at least one…/MEOX2 or ETV4).
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, rather treating cells derived from a glioblastoma patient.
However, Farouz teaches a method of treating a subject 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).
Regarding claim 10, 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, which corelates with reduction in malignancy. Therefore, one would be motivated to make the substitution for the advantage of knocking down known regulator genes such as MEOX2 in glioblastoma. The skilled artisan would have had a reasonable expectation that substituting the subject population from glioblastoma derived cells to glioblastoma in the method of Berezovsky would also result in knocking down MEOX2 in glioblastoma patients, and such method could be effective and work as predicted because Berezovsky 1) demonstrated knock down of MEOX2 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, and 25 - 27.
Claim 12 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 (claim 11) as applied to claims 8 – 11, 15, and 25 – 27 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 Non-Final Office Action of 9/12/2025 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 and one other master regulator, 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 MEOX-2 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 regulator is MEOX2 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 claim 12.
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 Non-Final Office Action of 9/12/2025 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.
Claim(s) 8 and 24 remain 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, which is cited on the IDS filed 08/12/2024, in view of Hugnot, (US 2014/0005249 -A1), hereinafter Hugnot, which is cited on the IDS filed 03/28/2022, as discussed in the Non-Final Office Action of 9/12/2025 and reiterated below.
Regarding reducing the expression and/or activity of a master regulator to a subject having glioblastoma of claim 8, Hugnot teaches administering an shRNA targeted to Nkx2.2 to a subject in need thereof, as a method of treating cancers such as glioblastoma (GBM) (abstract; claims 13 and 16; [0002, 0014, 0016]). This reads on an RNA interference agent that reduces expression of a master regulator as required by claim 8. Hugnot, further teach:
[0018]: it is now well documented that GBM
stem cells rely on a special set of genes (for instance Sox2,
Olig2, Bmi1 ... ) to maintain a high level of self-renewal.
These genes could be considered as potential targets to specifically
eliminate these cells.
Regarding claim 24, Hugnot teaches wherein the subject is human (GBM in humans, [0013]; human Nkx2.2, [0079]; in a patient in a need thereof, comprising the administration of a pharmaceutically effective amount of a pharmaceutical composition, [0178]).
Hugnot does not teach that the method inhibits or reduces the expression and/or activity of at least one master regulator selected from the group consisting of: ETV4, MLXIPL, MEOX2, DDN, and OTP (claim 8).
However, Berezovsky teaches knockdown of Sox2 in glioblastoma cells using shRNA reduced tumorigenicity of xenograft glioblastomas 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). Such knockdown results in reduced expression of MEOX2 and Nkx2.2 (master regulators) (page 203, left col. paragraph 1; Table W1).
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have substituted the agent that knocks down NKx2.2 in the method of administering an RNA interference agent resulting in knock-down of a master regulator to a glioblastoma subject as taught by Hugnot with an agent that knocks down Sox2 as taught by Berezovsky. It would have merely amounted to a simple substitution of prior art elements according to known methods to yield predictable results. One would be motivated to make the substitution for the advantage of knocking down known regulator genes such as MEOX2. The skilled artisan would have had a reasonable expectation that substituting the agent that knocks down NKx2.2 in the method of Hugnot with an agent that knock down of Sox2 could be effective and work as predicted because Hugnot 1) teaches that Sox2 is a target to knockdown in GBM; and 2) teaches that such targets may be knocked down by RNA interference agents and the same may be administered to a human patient. See MPEP 2143 I (B).
Thus, Berezovsky in view of Hugnot make obvious instant claims 8 and 24.
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
Applicants request clarification on the use of the reference of Fontanet for claim 11.
Clarification is: Fontanet is used as evidentiary reference to indicate (not reject) that PEA3, as used in Farouz, is ETV4. Recitation from rejection of claim 11 in the OA:
PEA3 is another name for ETV4 as evidenced by Fontanet (page 237, left col. paragraph 2).
Applicant's arguments filed 12/12/2025 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 argue:
Applicants essentially assert that: 1) there is no teaching provided to one of skill in the art to select MEOX2 or OTP from the extensive list of Sox2-regulated genes as they are each only mentioned in the applied ref of Berezovsky once: in Table W1; and 2) there is no teaching regarding administration to a subject. However, Applicants concede: Berezovsky encourages the skilled artisan to find other clinical solutions by 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). Perhaps here, Applicant is arguing about claim 26.
Specifically, the Remarks state that the secondary references e.g., Farouz, etc., is focused on a cell’s ability to differentiate, while Glioblastoma is only mentioned once in a list of over a hundred types of cancer.
Because of the vast number of choices provided in each of the references, 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; (C) which means 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 applicant's argument that (A) there is no motivation to combine the references, Examiner reiterates writing from the Office Action: 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). Even if as Applicants say, pertinent terms are mentioned only once, such is sufficient motivation to rely on the reference. Further, 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.”.
With respect to (B) there is no expectation of success, this is not found persuasive, as Applicants have not provided any reasoning as to why there would be no reasonable expectation of success in administering shRNA targeting the claimed genes to a glioblastoma patient, which is the scope of claims 8 – 11, 15, and 25 and 27. 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.
Claim 12, Berezovsky in view of Farouz, Chelban, and Amberger
Applicants argue 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.
Therefore, Examiner’s response remains the same as above.
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.
Claims 8 and 24, Berezovsky in view of Hugnot
Applicants argue Hugnot discloses shRNA targeted to Nkx2.2 to treat cancers but not ETV4, MLXIPL, MEOX2, DDN, and OTP to a subject having a glioblastoma.
Thus, Applicants argue 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.
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).
In the case of Hugnot, Hugnot was not used exclusively in the rejection of claims, rather a combination of Hugnot with Berezovsky was relied upon. Together, the references render obvious the recited method.
Applicants arguments are not dispositive, the rejection is maintained.
Conclusion
No claims allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence
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/SHABANA S MEYERING/Examiner, Art Unit 1635
/CATHERINE KONOPKA/Primary Examiner, Art Unit 1635