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 Group III (Claim 17 and new claims 18-20) in the reply filed on 07/28/2026 is acknowledged. The traversal is on the ground(s) that none of the prior art documents disclose treating pancreatic cancer or bile duct cancer patients by administering a substance that inhibits the ZIC5 protein, and applicant believes the invention of claims 17-20 should be examined without specifying the species. To expedite examination, Applicant elects a nucleic acid molecule that suppresses expression of the ZIC5 gene by RNA interferences as the substance, and if further election is required elects the nucleic acid molecule set forth in SEQ ID NO: 5 (siZIC5#1, Table 2). Applicant argues that the search and examination of all currently pending claims would not pose an undue burden on the Examiner and cites MPEP 803.
This is not found persuasive because this application is a 371 of PCT/JP2022/029163 and therefore the requirement for Unity of Invention is applied as stated in the Restriction Requirement and the Groups do not all require the same technical feature as stated in the Restriction Requirement. Applicants citation of MPEP 803 pertains to Restriction in Applications filed under 35 U.S.C. 111, which is not the case here, and therefore undue burden is also not a consideration
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 07/28/2026.
Claims 17-20 are under examination.
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 Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
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 incorporation-by-reference paragraph, 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.
Priority
This application is a 371 of PCT/JP2022/029163, filed 07/28/2022 and claims foreign priority to JAPAN 2021-126154, filed 07/30/2021 as reflected by the most recent filing receipt.
Information Disclosure Statement
The IDS dated 01/26/2024 has an error in the publication number of the U.S. Patent Application Publication listed as “20190062571” as Fukami et al. However, the correct number for Fukami et al. is “20190062751”. The publication number currently listed on this IDS is Lottenbach et al. and titled “Textiles Having Flame Protection Function”. Therefore the Examiner believes this is a typo in the number, and the Examiner has made the change in the number to 20190062751 on the IDS.
Appropriate correction is required.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See at least page 2 (paragraph 0003), page 33 (paragraph 0078), page 40 (paragraph 0095), citing browser-executable code.
Claim Objections
Claim 17 is objected to because of the following informalities: Claim 17 recites “ZIC5 protein” and “ZIC5 gene”. At least the first recitation of a protein or gene name should be fully recited for clarity rather than only the acronym of the protein/gene name (ZIC5). Appropriate correction is required.
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.
Written Description Rejection
Claims 17-20 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Instant claims 17-20 encompass administering to any subject an effective amount of a substance that reduces an intracellular content of a ZIC5 protein, wherein the substance is a genus of nucleic acid molecules (siRNA, shRNA, miRNA, etc.) that directly or indirectly suppresses the expression of the ZIC5 gene by RNA interference, or a genus of compounds represented by any of General Formulae (1) to (9) or a derivative thereof and which results in treating pancreatic or bile duct cancer.
Regarding the state of the art, Fukami et al. (US 20190062751, Published 28 Feb 2019), cited on an IDS, teach RNA-mediated Zic5 gene knockdown in cancer cells transfected with siZIC5#2 of SEQ ID NO: 6, “GGCTGTGACAAATCCTACA” (paragraphs 0145,0147) and results confirmed that a relative mRNA expression level of Zic5 gene was significantly reduced in the cells transfected with siZIC5#1 or siZIC5#2 (paragraph 0149), as well as shRNA, shZIC5-1 and shZIC5-2 of SEQ ID NOs: 11 and 12 respectively that reduces expression of the ZIC5 gene and suppressed tumor proliferation in the living body by Zic5 gene knockdown (Example 4, paragraphs 0172-0174). Fukami et al. teach the type of the tumor cell targeted by the tumor cell malignant transformation suppressor according to the present invention is not particularly limited, and examples thereof include cells of skin cancer, prostate cancer, thyroid cancer, lung cancer, breast cancer, liver cancer, pancreas cancer, bile duct cancer…(paragraph 0114).
While ZIC5 has been shown to be upregulated in many cancers, other than Fukami et al. cited above, the state of the art is limited in regard to the association of ZIC5 and pancreatic cancer and bile duct cancer and suppressing the expression of ZIC5 to treat pancreatic cancer and bile duct cancer.
The specification discloses chemicals, such as siZIC5#1 of SEQ ID NO: 5 and siZIC5#2 of SEQ ID NO: 6 (Example 1 and Table 2, pages 35-36, Example 2, page 38-39) that result in suppressing expression of ZIC5 gene and induce apoptosis in pancreatic cancer cells and bile duct cancer cells and suppress cell proliferation), and chemical compounds T-1 to T-12 (pages 42-43,Table 3) which reduce intracellular ZIC5 protein (paragraph 0103), and that compounds T-1 or T-2 induce apoptosis in pancreatic cancer cell and bile duct cancer cell line (Example 4, pages 45-46). However, the specification only shows the effect that T-1 and T-2 have as inducing apoptosis in pancreatic and bile duct cancer cells. Such effect has not been demonstrated for the other compounds, or derivatives thereof. Example 7 (pages 48-49) discloses a small hairpin RNA targeting ZIC5 in Table 4 of SEQ ID NO: 9 and which resulted in a decrease in proliferation rate of pancreatic cancer cells into which shZIC5 that suppresses ZIC5 was introduced, and Example 8 discloses reduction of tumor volume in vivo in a mouse transplanted with cancer cells containing shZIC5 and administered gemcitabine, and therefore the suppression of ZIC5 enhances sensitivity to gemcitabine and a synergistic effect is obtained.
Therefore, the specification discloses compounds which meet the written description and enablement provisions of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. However, as stated above, claims 17-20 are directed to encompass a genus of RNA interference nucleic acid molecules and derivatives of compounds of formula (1) to (9) which only correspond in some undefined way to specifically instantly disclosed chemicals, and therefore do not meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, due to lacking chemical structural information for what they are and chemical structures are highly variant and encompass a myriad of possibilities. This is not a representative number of nucleic acid molecules that suppress the expression of ZIC5 gene by RNA interference or a representative number of derivatives of the compounds of formula (1) to (9) the result in the function of treating pancreatic or bile duct cancer. The specification provides insufficient written description to support the genus encompassed by the claim. Note: MPEP 2163.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, (Fed. Cir. 1991), makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
Univ. of Rochester v. G.D. Searle, 69 USPQ2d 1886, 1892 (CAFC 2004), further supports this by stating that:
The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement. A description of an anti-inflammatory steroid, i.e., a steroid (a generic structural term) described even in terms of its functioning of lessening inflammation of tissues fails to distinguish any steroid from others having the same activity or function. A description of what a material does, rather than of what it is, usually does not suffice…. The disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described. (Emphasis added).
With the exception of the above specifically disclosed chemical structures (siZIC5#1 of SEQ ID NO: 5 and siZIC5#2 of SEQ ID NO: 6, compounds T-1 and T-2, and small hairpin RNA targeting ZIC5 of SEQ ID NO: 9), the skilled artisan cannot envision the detailed chemical structure of the encompassed RNA interference nucleic acid molecules and chemical compound derivatives of the recited compounds of formula 1 to 9, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. The chemical structure itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Circ. 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016, (Fed. Cir. 1991). In Fiddes v. Baird, 30 USPQ2d 1481, 1483, (Bd. Pat. App. & Int. 1993), claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence. Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 (Fed. Cir. 1997) held that:
...To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.
Furthermore, to the extent that a functional description can meet the requirement for an adequate written description, it can do so only in accordance with PTO guidelines stating that the requirement can be met by disclosing “sufficiently detailed, relevant identifying characteristics,” including “functional characteristics when coupled with a known or disclosed correlation between function and structure.” Univ. of Rochester v. G.D. Searle, 68 USPQ2d 1424, 1432 (DC WNY 2003). In the instant case, the specification has not shown a core-structure that achieves the recited effect or a structure-function correlation for the genus of nucleic acid molecules that suppresses expression of the ZIC5 gene by RNA interference or the derivatives of the compounds of formulas (1) to (9) and results in treating pancreatic cancer or bile duct cancer in a subject.
Therefore, only the above chemically structurally defined chemicals (siZIC5#1 of SEQ ID NO: 5 and siZIC5#2 of SEQ ID NO: 6, compounds T-1 and T-2, and small hairpin RNA targeting ZIC5 of SEQ ID NO: 9), but not the full breadth of the claim(s) meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. The species specifically disclosed are not representative of the genus because the genus is highly variant. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 USC § 112 is severable from its enablement provision. (See page 1115.)
Claim Rejections - 35 USC § 102/103
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 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.
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.
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.
Claims 17 and 18 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Fukami et al. (US 20190062751, Published 28 Feb 2019), and cited on an IDS.
Claim Interpretation: Instant claims 17 and 18 recite in the body of the claim, “administering to a subject an effective amount of a substance that reduces an intracellular content of a ZIC5 protein” and therefore encompasses administering to any subject. The subject is not limited to one with pancreatic or bile duct cancer as the body of the claim does not recite “administering to a subject in need thereof”. Regarding the instant claimed preamble of “A treatment method of pancreatic cancer or bile duct cancer comprising”, if the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020). See MPEP 2111.02. Therefore, for the 102(a)(1) rejection, art that recites the same method step as the body of the instant claims, reads on the instant claims, regardless of the instant preamble.
Regarding claim 17, Fukami et al. recites a method of treating prostate cancer comprising administering an effective amount of an anti-tumor agent to a subject, wherein the anti-tumor agent comprises a substance that suppresses or inhibits a Zic5 gene function as an active ingredient, and the substance inhibits expression of the Zic5 gene by RNA interference (claim 11). Fukami et al. teach RNA-mediated Zic5 gene knockdown in cancer cells transfected with siZIC5#2 of SEQ ID NO: 6, “GGCTGTGACAAATCCTACA” (paragraphs 0145,0147) and results confirmed that a relative mRNA expression level of Zic5 gene was significantly reduced in the cells transfected with siZIC5#1 or siZIC5#2 (paragraph 0149).
Alignment of instant siZIC5#1 of SEQ ID NO: 5 (Qy) with the siZIC5#2 of SEQ ID NO: 6 of Fukami et al. (Db) is shown below and is the identical siRNA sequence.
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Regarding claim 18, Fukami et al. teach ZIC5 is expressed in tumor cells (As the expression level of Zic5 gene becomes high in tumor cells, the E-cadherin expression is suppressed more, by which EMT occurs, and therefore malignant transformation is likely to occur. Conversely, in tumor cells in which the expression level of Zic5 gene became lower, the E-cadherin expression level does not decrease, by which EMT becomes unlikely to occur, and therefore malignant transformation is unlikely to occur. Therefore, the expression level of Zic5 gene in tumor cells is useful as a malignancy marker) (paragraph 0116) and teaches the type of tumor cell targeted by the tumor cell malignant transformation marker include cells of pancreas and bile duct cancer (paragraph 0114).
See above claim interpretation regarding the preamble and subject in the instant claims. Although the preamble in claim 11 of Fukami et al. recites a method of treating prostate cancer, it does not appear that the claim language or limitations in the body of the claim result in a manipulative difference in the method steps when compared to the prior art disclosure. See Bristol-Myers Squibb Company v. Ben Venue Laboratories, 58 USPQ2d 1508 (CAFC 2001). “It is a general rule that merely discovering and claiming a new benefit of an old process cannot render the process again patentable.” In re Woodruff, 16 USPQ2d 1934, 1936 (Fed. Cir. 1990). Granting a patent on the discovery of an unknown but inherent function would remove from the public that which is in the public domain by virtue of its inclusion in, or obviousness from, the prior art. In re Baxter Travenol Labs, 21 USPQ2d 1281 (Fed. Cir. 1991). See M.P.E.P. 2145. On this record, it is reasonable to conclude that the same patient is being administered the same active agent by the same mode of administration in the same amount (effective amount) in both the instant claims and the prior art reference. The fact that Applicant may have discovered yet another beneficial effect from the method set forth in the prior art does not mean that they are entitled to receive a patent on that method.
Thus, Fukami et al. teaches, either expressly or inherently implied, each and every limitation of the instant claims.
In the alternative, if the subject in the body of the instant claims were limited to someone with pancreatic cancer or bile duct cancer, Fukami et al. also teaches the type of the tumor cell targeted by the tumor cell malignant transformation suppressor according to the present invention is not particularly limited, and examples thereof include cells of skin cancer, prostate cancer, thyroid cancer, lung cancer, breast cancer, liver cancer, pancreas cancer, bile duct cancer…(paragraph 0114).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to arrive at a treatment method of pancreatic cancer or bile duct cancer comprising administering to a subject with pancreatic or bile duct cancer an effective amount of a substance that reduces an intracellular content of a ZIC5 protein, which is a ZIC5 siRNA of SEQ ID NO: 5 and wherein the pancreatic or bile duct cancer is a cancer in which the ZIC5 protein is expressed, based on the teachings of Fukami et al. with a reasonable expectation of success. There would be a reasonable expectation of success, because Fukami et al. pertains to cancer treatment, including pancreatic and bile duct cancer, and substances that inhibit expression of the Zic5 gene by RNA interference, including siRNA. One of ordinary skill in the art would have been motivated to do so because Fukami et al. taught that pancreatic cancer and bile duct cancer was included as the type of tumor cells targeted by the tumor cell malignant transformation suppressor of the invention and taught that siZIC5#2 of SEQ ID NO: 6, “GGCTGTGACAAATCCTACA” (paragraphs 0145,0147) significantly reduced relative mRNA expression level of Zic5 gene in the cells transfected with siZIC5#1 or siZIC5#2 (paragraph 0149).
Regarding the claimed “effective amount”, the amount of an active ingredient is a parameter that a person of ordinary skill in the art would routinely optimize based on the condition being treated, severity of the condition and desired dosing frequency, among other factors. It would have been obvious to one of ordinary skill in the art at the time of the invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). NOTE: MPEP 2144.05.
Accordingly, the limitations of claims 17 and 18 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
Claims 19 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Fukami et al. as applied to claims 17 and 18 above.
The teachings of Fukami et al. as applied to claims 17 and 18 have been described above.
Fukami et al. do not explicitly teach administering to a subject a combination a ZIC5 siRNA and an additional anti-cancer agent which is a BRAF inhibitor.
However, Fukami et al. teach the tumor cell malignant transformation suppressor and the like related to the present invention have an effect of suppressing malignant transformation and an anti-tumor effect even with respect to tumor cells which have BRAFV600E mutation and tumor cells which acquired a drug resistance to a BRAF inhibitor, vemurafenib, and thus are extremely effective novel drugs in tumor therapy (paragraphs 0044,0114). Fukami et al. teach examining whether ZIC5 changes sensitivity to the BRAF inhibitor (PLX4032, vemurafenib) (Example 7, paragraph 0209) Fukami et al. teach the influence of knockdown of endogenous ZIC5, and PDGFD and ITGA6, which are downstream factors, on a decrease in cell proliferation by PLX4032 and induction of apoptosis was examined. First, A375 cells were transfected with siNeg or siZIC5 described in Table 1, in the same manner as Example 1, and then treated with DMSO or PLX4032 solution, and that induction of apoptosis by PLX4032 was synergistically upregulated by Zic5, PDGFD, and ITGA6 knockdown, and that a decrease in the number of cells by PLX4032 treatment was promoted by Zic5, PDGFD, and ITGA6 knockdown (paragraph 0213).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date, to have modified the treatment method of Fukami et al. regarding administering an effective amount of an anti-tumor agent to a subject, wherein the anti-tumor agent comprises a substance that suppresses or inhibits a Zic5 gene function as an active ingredient, and the substance inhibits expression of the Zic5 gene by RNA interference and to administer an additional anti-cancer agent which is PLX4032 (a BRAF inhibitor) based on the teachings of Fukami et al. One of ordinary skill in the art would have been motivated to do so because Fumaki et al. taught the tumor cell malignant transformation suppressor and the like related to the present invention have an effect of suppressing malignant transformation and an anti-tumor effect even with respect to tumor cells which have BRAFV600E mutation and tumor cells which acquired a drug resistance to a BRAF inhibitor, vemurafenib, and taught transfecting cells with
siZIC5 described in Table 1 and PLX4032 solution, and that induction of apoptosis by PLX4032 was synergistically upregulated by Zic5, PDGFD, and ITGA6 knockdown, and that a decrease in the number of cells by PLX4032 treatment was promoted by Zic5, PDGFD, and ITGA6 knockdown (paragraph 0213). Therefore, one of ordinary skill in the art would have been motivated by these teachings and would be motivated to administer PLX4032 as a BRAF inhibitor to the subject that has been administered the Zic5 siRNA to increase apoptosis of the cancer cells.
Accordingly, the limitations of claims 19 and 20 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
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 17-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 10,669,545 (‘545), Issued 2 June 2020.
Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of ‘545 recites a method of suppressing tumor cell malignant transformation comprising suppressing or inhibitor a Zic5 gene function to suppress or inhibit acquisition of metastatic ability or acquisition of apoptosis resistance of a tumor cell, wherein the tumor cell is a melanoma or prostate cancer cell, and claim 2 of ‘545 recites suppressing or inhibiting the Zic5 gene function is carried out by inhibiting expression of the Zic5 gene by RNA interference. Claims 3 and 4 of ‘545 recite a method of treating melanoma and claim 5 recites a method of treating prostate cancer comprising administering an effective amount of an anti-tumor agent to a subject in need thereof, which is a substance that suppresses or inhibits a Zic5 gene function as an active ingredient, and claims 6 and 9 recite the substance suppresses or inhibits the Zic5 gene function by inhibiting expression of the Zic5 gene by RNA interference. Claims 10-12 of ‘545 recite species inhibitors of Zic5 which are small interfering RNA, short hairpin RNA, and miRNA.
As instant claims 17-20 do not limit the patient population to those with pancreatic or bile duct cancer in the body of the claim (recites “administering to a subject an effective amount of a substance that reduces an intracellular content of a ZIC5 protein, wherein the substance is a nucleic acid molecule that suppresses the expression of the ZIC5 gene by RNA interference), the claims are not patentably distinct from each other and recite the same active method steps.
Conclusion
Claims 17-20 are rejected.
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/STEPHANIE L SULLIVAN/Examiner, Art Unit 1635
/ABIGAIL VANHORN/Primary Examiner, Art Unit 1636
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