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 .
Detailed Action
Pursuant to a preliminary amendment filed on August 16, 2024, claims 1, and 3 - 12 are currently pending in the instant application. Claims 1 and 7 are independent claims, and claim 2 is canceled.
Therefore, claims 1 and 3 – 12 are under consideration to which the following grounds of rejection are applicable. Claims 1 and 7 are independent claims.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on August 16, 2024 and June 2, 2026 has been considered. An initialed copy of the IDS accompanies this Office Action.
Priority
The present application filed August 16, 2024, is a 35 U.S.C. 371 national stage filing of International Application No. PCT/JP2023/006197, filed February 21, 2023, which claims the benefit of JP2022-025008, filed February 21, 2022.
Acknowledgment is made of Applicant's claim for foreign priority based on JP2022-025008, filed February 21, 2022. The applicant has submitted the certified untranslated copy of the foreign priority application on August 16, 2024.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non- English application.
Claim Rejection - 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 3 - 12 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 is indefinite for the recitation of “major ingredient” in line 2. “Major” is a relative term that renders the claim indefinite. It is unclear how much of the inhibitor is present, and also what other ingredients are present. Thus, the metes and bounds of the claim cannot be determined.
Claims 1 and 8 are indefinite in the recitation of the relative term “enhancing”. The term " enhancing " is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Appropriate action is required.
Claims 1, 3 – 6, 8, and 10 – 12 are is indefinite for the recitation of “an inhibitor against a protein involved in the DNA damage response,” such as recited in claim 1, line 2. Viral vectors can be of either DNA or RNA, and thus, it is unclear how an inhibitor against a protein involved in the DNA damage response can be used in an RNA viral vector. Thus, the metes and bounds of the claim cannot be determined.
Claims 7 is rejected as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are, for example: “producing an engineered immune cell by the steps of x, y and z.” it is noted that claim 7 recites the steps of producing a viral vector, comprising culturing a viral vector producing cells in which a protein involved in the DNA damage response is inhibited, but does not recite the steps of culturing the cells the virus to product the viral vector producing cells. A claim that does not set forth any steps involved in the method/process is unclear as to what method/process applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
Claim 8 is indefinite in its recitation of “ a viral vector” in line 3. Claim 8 depends on claim 7 which requires “the viral vector” in line 3. It is unclear is the viral vector in claim 8 is the same vector or a different one.
Claim 8 is indefinite in its recitation of “the cell” in line 2. There is not proper antecedent bases for the “cell”. Claim 7 recites “J! viral vector-producing cells “. Appropriate correction is requested.
Claim Rejection - 35 USC § 112(a) Scope of Enablement
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 7 - 12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the Specification, while being enabling for
a method for producing a viral vector comprising culturing a viral vector producing cells in which the cell comprising a siRNA targeting CHEK1 or a siRNA targeting AURKA is administered with cyclopiazonic acid (referred to as substance D in the disclosure),
does not reasonably provide enablement for using any protein involved in the DNA damage response is inhibited or the cell that does not comprise a siRNA targeting CHEK1 or AURKA.
The Specification does not enable any person skill in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. The claims, when given the broadest possible interpretation, encompass a method for producing a viral vector comprising culturing a viral vector producing cells in which a protein involved in the DNA damage response is inhibited, and collecting the viral vector from the cultured cells. The Specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the patent coupled with information known in the art without undue experimentation (United States v. Telectronics, Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is required is not based on a single factor but is rather a conclusion reached by weighing many factors (See Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter, 1986) and In re Wands, 8USPQ2d 1400 (Fed. Cir. 1988); these factors include the following:
Nature of invention. The invention encompasses a method for producing a viral vector comprising culturing a viral vector producing cells in which a protein involved in the DNA damage response is inhibited, and collecting the viral vector from the cultured cells.
Scope of the invention. The invention is for enhancing the production of viral vectors using viral vector-producing cells in which a protein involved in the DNA damage response is inhibited.
Number of working examples and guidance. In the instant case, Applicant provides two
relevant working examples. The disclosure teaches Fig. 13, which shows the results of combination Example 1 (Paragraph [0108]). Fig. 13 teaches the effects of enhancing production of AAV vectors were improved to a significant extent with the use of the inhibitor against the serine/threonine kinase Chk1 in combination with the inhibitor against the sarcoplasmic reticulum Ca.sup.2+-ATPase (Paragraph [0109]). This example only teaches the use of the Chek1 siRNA with the inhibitor against the sarcoplasmic reticulum Ca.sup.2+-ATPase, specifically cyclopiazonic acid.
Similarly, Fig. 14 teaches the effects of enhancing production of AAV vectors were improved to a
significant extent with the use of the inhibitor against the Aurora kinase in combination with the inhibitor against the sarcoplasmic reticulum Ca.sup.2+-ATPase (Paragraph [0110]). This example only teaches the use of the Aurora kinase siRNA with the inhibitor against the sarcoplasmic reticulum Ca.sup.2+-ATPase, specifically cyclopiazonic acid.
No other examples are taught using any other siRNAs in combination with any other proteins that inhibit the DNA damage response.
State of the art. Although the field of viral vectors is highly developed, the method for
producing a viral vector comprising culturing a viral vector producing cells in which a protein involved in the DNA damage is inhibited is not highly developed. The art must therefore be considered to be poorly developed.
Unpredictability of the art. Before the effective filing date of the claimed invention, it was
known in the art that the inhibition of Chk1 resulted in decreased replication of the BKPvY DNA and viral spread, as taught by Hainley et al. (Hainley LE et al. Viruses. 2021 Jul 13;13(7):1353. doi: 10.3390/v13071353. PMID: 34372559; PMCID: PMC8310304) (Abstract).
Further, it was known in the art that porcine kidney epithelial PK 15 cells were virulent wild-type PRV strain, and then cultured with thapsigargin (Tg), wherein low concentration of Tg treatment significantly increased PRV replication and virus yield, and high concentration of Tg significantly inhibited PRV replication and virus yield (pg. 6, left column, first paragraph), as evidenced by Yang et al. (Yang S. et al, Vet Microbiol. 2019 Dec;239:108485. doi: 10.1016/j.vetmic.2019.108485. Epub 2019 Oct 31. PMID: 31767094). (This reference is listed in the IDS filed August 16, 2024). This reference teaches the variability in using thapsigargin for impacting virus yield.
Additionally, it was known in the art that F13, K17, and H17 increase the transduction levels of various AAV serotypes, wherein the enhancement in transduction was confirmed after knockdown of AURKA, AURKB, PLK1, and PTK2, as evidenced by Maddalena et al. (Maddalena A. et al. Hum Gene Ther. 2018 Aug;29(8):886-901. doi: 10.1089/hum.2017.220. Epub 2018 Jul 5. PMID: 29641320; PMCID: PMC6098407) (pg. 898, right column, third paragraph). (This reference is listed in the IDS filed August 16, 2024). This reference teaches that the genes need to be knocked down along with the introduction of the inhibitors to yield an increase in viral transduction.
Amount of Experimentation Required. Given the unpredictability of the art pertaining to
the role in the inhibitors in enhancing production of the viral vectors, the variability in the inhibitors, and the relevance of concentration in increasing the virus yield, the skilled artisan would have to conduct undue, and unpredictable experimentation to practice the claimed invention proteins involved in the DNA damage response, and produce the viral vectors. Further, due to the lack of specific guidance in the specification for expressing all the inhibitors and siRNA in the cells, it would require undue experimentation to practice the breadth of the instant methods as claimed.
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3, 6, 7, 8, and 12 are rejected under 35 U.S.C. 102 (a)(1)/(a)(2) as being anticipated
by Perez-Olais et al. (hereinafter referred to as “Olais”) (Pérez-Olais et al. Virus Res. 2019 Dec;274:197777. doi: 10.1016/j.virusres.2019.197777. Epub 2019 Oct 15. PMID: 31626875.). This reference is listed in the IDS filed August 16, 2024.
Regarding claims 1, 3, 6, 7, 8, and 12, Olais teaches the role of AurKB during Denv 2 infection using the specific AurKB inhibitor, ZM 447439, wherein the inhibition of AurKB induced a reduction in viral particle production without an alteration in viral translation and replication (pg. 2, left column, third paragraph) (interpreted as the agent for enhancing production of viral vectors against Aurora kinase is an analog). (Please note: the as-Filed Specification that ZM447439 is an example of inhibitor against the Aurora kinase (Paragraph [0065]).
Claims 3 and 4 are rejected under 35 U.S.C. 102 (a)(1)/(a)(2) as being anticipated
by Zitvogel et al. (hereinafter referred to as “Zitvogel”) (US 20130052160 A1, published February 28, 2013).
Regarding claims 3 and 4, Zitvogel teaches the product stimulating the autophagy machinery is thasigargin (claim 25). It is noted that, if the prior art discloses identical chemical structure, the properties applicant discloses and/or claims are necessarily present, In re Spada, 911 F.2d 705, 709, 15 USPQ2d. As such any functional limitations would be present in the identical compounds taught by Zitvogel et al. Therefore the product of Zitvogel anticipates the instant claims.
Claims 3 and 5 are rejected under 35 U.S.C. 102 (a)(1)/(a)(2) as being anticipated
by Dmello et al. (hereinafter referred to as “Dmello) (US 20210145965 A1, published May 20, 2021).
Regarding claims 3 and 5, the inhibitor comprises AZD7762 (claim 5). It is noted that, if the prior art discloses identical chemical structure, the properties applicant discloses and/or claims are necessarily present, In re Spada, 911 F.2d 705, 709, 15 USPQ2d. As such any functional limitations would be present in the identical compounds taught by Dmello et al. Therefore the product of Dmello anticipates the instant claims.
Conclusion
Claims 1, 3 - 12 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VYOMA SHUBHAM TIWARI whose telephone number is (571)272-2954. The examiner can normally be reached M-F 8:30 - 5:30 EST.
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/VYOMA SHUBHAM TIWARI/Examiner, Art Unit 1634
/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634
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