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
Applicant's election with traverse of claims 4 and 8-9 in the reply filed on May 26, 2026 is acknowledged. The traversal is on the ground(s) that the claims make a contribution over Radin, whose teachings relate to “a completely different biological system” from the claimed invention. This is not found persuasive because it is an objective fact that a “GluA knockdown agent” that kills glioma cells was already known in the prior art of Radin, wherein claim 1 of the instant application, for instance, does not recite any specific type of “biological system”. Claim 1 merely recites a biological entity comprising an “anti-tumor transgene” that is a “GluA knockdown agent.” Applicant further argues that search and examination of group I would overlap with those of group II thus there is no “undue burden on the examiner” to search and examine all claims. In response, applicant’s attention is directed to the fact that a burden issue is not a criterion for 371 national stage applications. Hence, applicant’s argument is irrelevant.
The requirement is still deemed proper and is therefore made FINAL.
Status of Claims
Claims 1-9 are currently pending in the instant application. Claims 2-3 and 6-7 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Accordingly, claims 1, 4-5, and 8-9 are under examination on the merits in the instant application.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on November 3, 2023, March 19, 2026, and June 11, 2026 have been considered by the examiner. Note that NPL Citation No. 4 filed on June 11, 2026 is considered only insofar as the English language title and abstract as provided in the copy submitted by applicant.
Specification
The disclosure is objected to for containing sequence rule non-compliant subject matter. See paragraph 00038. Appropriate correction is required as instructed below.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – The nucleotide sequences appearing in the specification, see paragraph 00038, is not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Objections
Claims 4 and 8 are objected to because of the following informalities: “protein, an” in line 2 should be “protein and an”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 4 and 8-9 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.
Claims 4 and 8 each recite “an immune response promoter in the form of an anti-PD-1 antibody, an anti-CTLA-4 antibody”.
The accepted meaning of the term “promoter” in the relevant art is generally understood in relation to a nucleotide sequence that is operably linked to a transgene sequence, wherein the nucleotide sequence promotes transcription of the transgene sequence. Indeed, the instant specification discloses the term “promoter” in “ICP47 gene promoter” or “ICP47-HSV-11 promoter”. Note that the specification does not redefine the term “promoter” to mean something else other than the art-accepted meaning. As such, it is unclear what the “promoter” means in claims 4 and 8 and how the “promoter” as accepted and understood in the relevant art can possibly in the “antibody” form. Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “promoter” or “immune response promoter” is indefinite because the specification does not clearly redefine the term.
Solely in the interest of compact prosecution, the phrase “an immune response promoter in the form of” will not be taken into consideration.
Claim 8 recites the limitation "wherein the anti-tumor transgenes" in plural term in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. Note that claim 5 recites “anti-tumor transgene”.
Claim 9 recites the limitation "wherein the vector" in line 1. There is insufficient antecedent basis for this limitation in the claim.
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.
Claims 1, 4-5, and 8 are 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This includes a new matter rejection.
Claims 1, 4-5, and 8 as broadly written require any “knockdown agents” targeting AMPA receptor subunits thereby providing “AMPA receptor interference” and “anti-tumor transgene”, which is “effective in killing human glioblastoma cells”. The instant claims are completely silent regarding the structure of the claimed “agent” or “agents” having the function of “knockdown” and “interference” of at least one AMPA receptor subunit, wherein the agent/agents have an “anti-tumor” function in human glioblastoma cells. That is, the claims recite the “agents” only in terms of function. As such, the claimed limitation of “agent” or “agents” encompasses a myriad of structurally diverse agents in various different classes including agents (e.g., siRNA, shRNA) mediating RNA interference, antibodies, peptides, small molecules, and so forth. In contrast to the instantly claimed broad genus of the “knockdown agents” that should be “anti-tumor”, it appears that the instant specification at best describes a single species of agents: “a C-terminal fragment of GluA1” and “a C-terminal fragment of GluA2”. See paragraphs 00034-00035. The peptide species for each of GluA1 knockdown agent and GluA2 knockdown agent is not a representative number of the entire genus of “anti-tumor” agents claimed without any structural limitations because the actual “knockdown” and “interference” function leading to “killing human glioblastoma cells” for structurally different species other than the C-terminal fragment peptide species cannot be extrapolated based on the disclosed C-terminal fragment peptides. Hence, the instant specification fails to disclose a representative number of species reflecting the structural variation encompassed by the broad claims in the instant case, thereby failing to reasonably convey that the instant inventor had possession of the entire genus of the “agents” as of the filing date sought in the instant case.
In addition, claims 5 and 8 require that the “vector” should comprises “a wild-type HSV-1 virus”. However, it is noted that the HSV-1 virus included in a vector encoding an anti-tumor transgene is at best described as being a mutant, ICP 34.5-deleted, oncolytic virus, not the instantly required “wild-type” virus. See for instance paragraph 00013 disclosing that the “new OV is an HSV-1 having its ICP34.5 gene deleted”. Further, the instant specification does not adequately describe the required function of “killing human glioblastoma cells” by the instantly required “wild-type” HSV-1 virus-containing vector. That is, the specification fails to describe the requisite structure-function correlation for the instantly claimed vector required to comprise a “wild-type HSV-1 virus”. Therefore, the instant specification not only introduces new matter that is not described in the specification but also fails to reasonably convey that the instant inventor had possession of the claimed wild-type HSV-1 virus-containing vector “that is effective in killing human glioblastoma cells”.
Solely in the interest of compact prosecution, the claimed “HSV-1 virus” will be interpreted as a non-wild-type HSV-1 virus.
Claim 8 recites that the vector comprises “an IL2.” The instant specification is completely silent regarding “IL2”, let alone a vector comprising “IL2” in addition to other elements recited in the claim. Accordingly, claim 8 introduces new matter that is not supported by the specification as originally filed.
Solely in the interest of compact prosecution, “IL2” will be interpreted as “IL12.”
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by de Groot et al. (Journal of Neuro-Oncology, 2008, 88:121-133, applicant’s citation).
de Groot discloses a construct encoding an shGluR1 that interferes with GluR1 expression by RNA interference, wherein the construct inhibits the growth of human glioblastoma cells in xenograft mice. See pages 127-130; Figure 6; title.
Accordingly, claim 1 is described by de Groot et al.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Radin et al. (International Journal of Molecular Sciences, 2020, 21:1-17, of record).
Radin teaches that each of Glur1 and Glur2 plays an “oncogenic role” in glioma by reporting that dominant negative (DN)-Glur2 expression in glioma cells in xenograft mice resulted in increased survival. See pages 2 and 4-5.
Accordingly, claim 1 is described by Radin et al.
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.
Claims 1, 4-5, and 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over de Groot et al. (Journal of Neuro-Oncology, 2008, 88:121-133, applicant’s citation) in view of Radin et al. (International Journal of Molecular Sciences, 2020, 21:1-17, of record), Saha et al. (Cancer Cell, 2017, 32:253-267), and Coffin (WO 2019/243847 A1).
de Groot discloses a construct encoding an shGluR1 that interferes with GluR1 expression by RNA interference, wherein the construct inhibits the growth of human glioblastoma cells in xenograft mice. See pages 127-130; Figure 6; title.
de Groot does not teach a construct or a vector comprising agents each knocking down GluR1 and GluR2, a fusogenic protein, an anti-PD-1 antibody, an anti-CTLA-4 antibody, and an IL12.
Radin teaches that each of Glur1 and Glur2 plays an “oncogenic role” in glioma by reporting that dominant negative (DN)-Glur2 expression in glioma cells in xenograft mice resulted in increased survival and that GluR1 is expressed in glioma tumor microtubes (TMs) in neuro-glioma synapses (NGS) and is strongly correlated with “intratumoral connectivity”, wherein AMPA-receptor-mediated synaptic input via TMs “results in glioma invasiveness and growth.” See pages 2 and 4-5.
Saha teaches that an oncolytic herpes simplex virus (oHSV) expressing “a triple combination” of “IL-12 and two immune checkpoint inhibitors, anti-PD-1 and anti-CTLA-4 antibodies” is useful for inhibiting GBM growth. See pages 253-254, 258, and 264.
Coffin teaches making “oncolytic viruses expressing a fusogenic protein and at least one immune stimulatory molecule” for the purpose of treating “glioma”, wherein oncolytic virus is “HSV1” that is deficient in functional ICP34.5, the fusogenic protein is a “glycoprotein from gibbon ape leukemia virus (GALV)”, and the immune stimulatory molecule is “an antibody or a fragment thereof which binds CTLA-4”, wherein the oncolytic virus encoding the fusogenic protein and the anti-CTLA-4 antibody can be used concurrently in combination with an anti-cancer, immune co-inhibitory pathway antagonist, which is an “PD-1 inhibitor” that is an antibody. See claims 1-7, 14-18, 21-22, and 34-37.
Coffin teaches, “Expression of fusogenic protein(s) by the virus can further enhance viral spread through tumors. Expression of fusogenic protein(s) by the virus can further enhance tumor cell killing.” See pages 7-8.
It would have been obvious to one of ordinary skill in the art before the effective filing date to further incorporate Radin’s dominant negative-GluR2, Saha’s “triple combination”, and a fusogenic protein of Coffin into de Groot’s construct comprising an shRNA targeting GluR1 and to formulate the combined elements in an oncolytic HSV-1 lacking functional ICP34.5. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in order to enhance the potency and efficacy of Radin’s anti-human glioblastoma composition because making a combination composition, especially in the form of an oncolytic HSV-1 comprising one or more of IL-12, an PD-1 antibody, an CTLA-4 antibody, and a fusogenic protein was an art-recognized goal and methodology for making an anti-human glioblastoma composition as evidenced by the teachings of Saha and Coffin, and because both GluR1 and GluR2 were taught to play an oncogenic role in glioblastoma as taught by Radin, which therefore would have reasonably suggested advantages in inhibiting both GluR1 and GluR2 for additive or greater anti-glioblastoma effects. Therefore, the instantly claimed subject matter is nothing but a mere combination of well-known, art-recognized agents known to be useful for inhibiting glioblastoma cells either as a single agent or as a combination agent.
Accordingly, claims 1, 4-5, and 8-9 taken as a whole would have been prima facie obvious before the effective filing date.
Conclusion
No claim is allowed.
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/DANA H SHIN/Primary Examiner, Art Unit 1635
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