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 December 26, 2024, claims 1 - 8 are currently pending in the instant application.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on November 25, 2024 has been considered. An initialed copy of the IDS accompanies this Office Action.
Priority
The present application filed November 25, 2024, is a Divisional Application of 16/755,453, filed on April 10, 2020 (now US Patent 12188036), which claims benefit of a 35 U.S.C. 371 national stage filing of International Application No. PCT/KR2018/011953, filed October 11, 2018; which claims benefit of Korea Application KR10-2017-018858, filed October 11, 2017.
Filing of a certified untranslated copy of the KR10-2017-018858, filed April 10, 2020, in parent application 16/755453 is acknowledged.
Thus, the earliest possible priority for the instant application is October 11, 2017.
Nonstatutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1 - 8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 14 of application 16755453 (published as US20220299721 A1, published September 24, 2020). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are wholly encompassed by, and significantly overlap in scope with claims 1 – 8 of instant application 18959294.
Claim 1 of 16755453 is directed to an expression cassette for production of a target protein, comprising a promoter, a polynucleotide coding for the target protein, an intronic RNA sequence and a poly A sequence, wherein the intronic RNA sequence comprises a splicing donor, a branch and a splicing acceptor.
Claim 6 of 16755453 teaches that the expression cassette, teaches a list of target genes (including CXCR4, PDK4, and MAPK3).
Claim 7 of 16755453 teaches that the intronic RNA sequence is selected from the group consisting of shRNA, miRNA, stRNA…snRNA.
Claim 9 of 16755453 teaches the miRNA sequence for target gene regulation is miR483 represented by any one of SEQ ID NOS: 34 to 36.
Claim 1 of the instant application is directed to an expression cassette for production of a target protein, comprising a promoter, a polynucleotide coding for the target protein, an intronic RNA sequence and a poly A sequence, wherein the intronic RNA sequence comprises a splicing donor, a branch and a splicing acceptor, and wherein the target gene expression regulation RNA sequences comprises one or more miRNA sequences.
Claim 5 of the instant application teaches that the target gene is selected from the group consisting of CXCR4, PDK4, and MAPK3.
Claim 6 of the instant application teaches the miRNA sequence for target gene regulation is miR483 represented by any one of SEQ ID NOS: 34 to 36.
Therefore, the instant application is in essence a “species” of the generic invention of 16755453. It has been held that a generic invention is “anticipated” by a “species” within the scope of the generic invention. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
Please note: The examiner acknowledges that the instant application is a divisional of application 16755453. However, in the restriction was sent out on 6/23/2023 with the Appl 16/755,453, the claims of the patent and the instant claims are directed to the same invention, an expression cassette for the production of a target protein. Thus, the nonstatutory double patenting rejection is appropriate.
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 1 – 8 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
An expression cassette for production of a target protein, comprising a single promoter, a polynucleotide coding for the target protein, a polynucleotide sequence encoding an intronic RNA sequence and a poly A sequence, wherein the intronic RNA sequence comprises a splicing donor, a branch, and a splicing acceptor, and a target gene expression regulation RNA sequence, and wherein the target gene expression regulation RNA sequence comprises one or more miRNA sequences,
wherein the target protein is an antibody or a fragment thereof;
wherein the single promoter transcriptionally links the polynucleotide coding for the target protein and the polynucleotide sequence encoding the intronic RNA;
and wherein the target gene expression regulation RNA sequences a miRNA selected from the group consisting of miR483 represented by any one of Seq ID Nos: 34 – 36,
does not reasonably provide enablement for any target proteins, or the use of any target gene expression regulation RNA sequence.
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 an expression cassette for production of a target protein, comprising a promoter, a polynucleotide coding for the target protein, a polynucleotide sequence encoding an intronic RNA sequence and a poly A sequence, wherein the intronic RNA sequence comprises a splicing donor, a branch, and a splicing acceptor, and a target gene expression regulation RNA sequence, and wherein the target gene expression regulation RNA sequence comprises one or more miRNA (micro RNA) sequences. 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 An expression cassette for production of a target protein, comprising a promoter, a polynucleotide coding for the target protein, a polynucleotide sequence encoding an intronic RNA sequence and a poly A sequence, wherein the intronic RNA sequence comprises a splicing donor, a branch, and a splicing acceptor, and a target gene expression regulation RNA sequence, and wherein the target gene expression regulation RNA sequence comprises one or more miRNA (micro RNA) sequences.
Scope of the invention. The invention encompasses an expression cassette for production of a high expression and high functionality target protein by regulating expression of an endogenous gene.
Number of working examples and guidance. In the instant case, Applicant teaches one relevant example. In the disclosure, example 1 teaches the manufacture of an intron sequence, wherein the intron sequence has the following construction: SD + miR483 target miRNA + branch + SA, referring to Seq ID No: 34 – 36 (Paragraph [0095] and Table 1). This example does not teach the use of any other miRNAs in the intron sequence. This intronic sequence was then used in the construction of an expression cassette, as shown in Table 2.
State of the art. Although the field of expression cassettes for production of target protein
is well known in the art, the expression cassette comprising an intronic RNA sequence, which comprises a target gene regulation RNA sequence, along with the promoter, polynucleotide encoding for the target protein, 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 miRNAs can be used to target multiple genes and pathways is a promising cell-engineering strategy to increase recombinant protein production in mammalian cells, as evidenced by Loh et al. (Loh WP. Et al. Overexpression of microRNAs enhances recombinant protein production in Chinese hamster ovary cells. Biotechnol J. 2014 Sep;9(9):1140-51. doi: 10.1002/biot.201400050. Epub 2014 Jun 23. PMID: 24819042.). Loh et al. identified miRs-17, -19b, -20a, and -92a to be differentially expressed between high- and low- monoclonal antibody-producing Chinese hamster ovary (CHO) cell clones, and thus can be used as miRs-17, -19b, and -92a as cell-engineering targets to increase recombinant protein production in mammalian cells (Abstract). This reference teaches the use of different miRNAs that are used to increase recombinant protein production.
Additionally, it was known in the art that antibody-producing Chinese-hamster ovary cells (CHO-DG44) were converted into cells producing antibodies with strongly enhanced ADCC (antibody-dependent cellular cytotoxicity) by knocking down FuT8 (α-1,6-fucosyltransferase or fucosyltransferase 8) via constitutive expression of shRNA (short-hairpin RNA) against FuT8, as evidenced by Beuger et al. (Beuger V. et al. Short-hairpin-RNA-mediated silencing of fucosyltransferase 8 in Chinese-hamster ovary cells for the production of antibodies with enhanced antibody immune effector function. Biotechnol Appl Biochem. 2009 May;53(Pt 1):31-7. doi: 10.1042/BA20080220. PMID: 19032154.) (Abstract). This reference teaches that the antibodies production was enhanced using shRNAs (not miRNAs).
Amount of Experimentation Required. Given the unpredictability of the art pertaining to
the particular miRNAs that are used to increase protein production, and the use of shRNAs that are being used to enhance antibody (i.e. target protein) production, the skilled artisan would have to conduct undue, and unpredictable experimentation to practice the claimed invention using the expression cassette.
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, and 4 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Powell et al. (hereinafter referred to as “Powell”) (Powell SK et al. Viral expression cassette elements to enhance transgene target specificity and expression in gene therapy. Discov Med. 2015 Jan;19(102):49-57. PMID: 25636961; PMCID: PMC4505817.)
Regarding claims 1, Powell teaches an AAV vector used for regulating transgene expression levels, comprising a promoter, intron, transgene, and poly A sequences (Introduction Paragraph 2, and Figure 1) (interpreted as an expression construct for production of a target protein, comprising a promoter, an intronic RNA sequence, a polynucleotide coding for the target protein (i.e. transgene), and a poly A sequence, instant claim 1). Powell teaches an intron sequence between the promoter and the single transgene (Figure 1) (interpreted as an intronic sequence between a promoter and a polynucleotide coding for the target protein, instant claim 4 and at least one intronic RNA sequence on a single target protein expression cassette, instant claim 3). Powell teaches that the introns contains a splice donor and splice acceptor (Table 3) (interpreted as the intronic RNA sequence containing a splicing donor, and splicing acceptor, instant claim 1).
Further regarding claim 1, Powell teaches that the vector comprises miRNA target sequences, which are sequences complementary to endogenous miRNA used to inhibit transgene expression (Figure 1, and Endogenous MicroRNAs) (interpreted as an RNA sequence for target gene expression regulation, instant claim 1). Powell teaches the use of miR-142-3pT, miR-122aT, and miR-124 in the expression vectors (Endogenous MicroRNAs).
Powell does not specifically exemplify that the target protein is antibody (instant claim 2), the target genes exemplified in claim 5 (instant claim 5), the miRNA sequences represented by Seq ID Nos 34 – 38 (instant claim 6), and sequences of the splicing donor, branch, and splicing acceptor (instant claim 7), and the antibody expression level (instant claim 8).
Powell meets all the limitations of the claims and, therefore, anticipates the claimed invention.
Claim Rejection - 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 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.
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.
Claims 1 and 2 are rejected under 35 U.S.C. 103 as being unpatentable over Powell as applied to claims 1, 3 and 4above, and further in view of Kim et al. (hereinafter referred to as “Kim”) (US Patent US 11,046,975 B2. Published: June 29, 2021; priority date: April 16, 2015).
The teachings of Powell with regard to claims 1, are described supra.
Powell does not specifically exemplify that the target protein is antibody (instant claim 2), the target genes exemplified in claim 5 (instant claim 5), the miRNA sequences represented by Seq ID Nos 34 – 38 (instant claim 6), and sequences of the splicing donor, branch, and splicing acceptor (instant claim 7), and the antibody expression level (instant claim 8).
Regarding claim 2, Kim teaches an expression vector for antibody expression, comprising a promoter, and intron, and antibody gene, and a poly A sequence (claim 1) (interpreted an expression vector wherein the target protein is an antibody, instant claim 2).
A person of ordinary skill in the art would have had a reasonable expectation of success in substituting the transgene that is expressed using the AAV vector, as taught by Powell, for the antibody that is expressed using an expression vector, as taught by Kim, because both use expression cassette to express proteins, and the expression cassette comprise similar components. Therefore, these compositions are functional equivalents in the art, and substituting one for the other would have been obvious at the time of the invention. “When a patent ‘simply arranges old elements with each performing the same function it had been known to perform’ and yields no more than one would expect from such an arrangement, the combination is obvious.” See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007) at 1395-1396, quoting Sakraida v. AG Pro, Inc., 425 U.S. 273 (1976) and In re Fout, 675 F.2d 297, 301 (CCPA 1982) (“Express suggestion to substitute one equivalent for another need not be present to render such substitution obvious”).
Therefore, in view of the benefits of inducing stable gene expression in mammalian cells as exemplified by Kim, it would have been prima facia obvious for one of skill in the art before the effective filing date of the claimed invention to modify the method of transgene regulation in the cell as disclosed by Powell to include the methods of a biscistronic expression cassette to express an antibody as taught by Kim with a reasonable expectation of success in expressing high yields of the light and heavy chains of the antibody in the cell. It would have been prima facia obvious to combine the cited references because Powell teaches an expression vector comprising a promoter, intron, transgene, and poly A sequences; and Kim teaches an expression vector comprising a promoter, intron, antibody, and poly A sequences.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly rejected under 35 USC §103 as obvious over the art.
Claims 5 - 8 are free of prior art.
Conclusion
Claims 1- 8 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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