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
The amendment filed June 23, 2025 in response to the Office Action of December 23, 2024 is acknowledged and has been entered.
Claims 1-3, 7-11 have been amended.
Claims 1-3 and 7-11 are currently under consideration as drawn to the elected invention.
Priority
Acknowledgement has been made that this application claims priority to foreign applications: JP 2017-127973, filed 2017-06-29.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more amended claims of this application. Examiner has established a priority date of July 24, 2023 for amended claims 1-3 and 7-11 because the amended claims as currently constituted recite: “a method for removing suppression of anti-tumor immunity caused by a tumor cell, comprising suppressing expression of Slug gene in the tumor cell with a nucleic acid hybridizing to the Slug gene to remove suppression of anti-tumor immunity by cytotoxicT cells, wherein in the tumor cell,a tyrosine residue(s) at the 111-th position and/or the 249-th position of human IDO1, or a tyrosine residue(s) of non-human IDO1 at a position(s) corresponding to the 111-th position and/or the 249-th position of human IDO1 is/are phosphorylated; and/or an aryl hydrocarbon receptor (AhR) is activated” and a review of the parent applications does not reveal the broadly claimed methods (also see 112(a) rejection below). Applicant is invited to submit evidence pointing to the serial number, page and line where support can be found establishing an earlier priority date.
NEW REJECTION
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 1-3 and 7-11 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.
Claim 1 was amended after the filing date. The limitation of “suppressing expression of Slug gene in the tumor cell with a nucleic acid hybridizing to the Slug gene” in claim 1 has no clear support in the specification as originally filed. Applicants argue in the Remarks filed June 23, 2025 that support for the limitation can be found throughout the original specification and claims, at least in paragraphs [0021] and [0038] of the specification.
Paragraph [0021] states:
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Paragraph [0038] states:
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Examiner could not find support for the limitation in the original specification, including paragraphs [0021] and [0038] of the specification. The original specification discloses suppressing expression of Slug gene using one specific shRNA to Slug in MCA205 overexpressing AhR (Figs. 11-13, and Example 5). The introduction of claim changes which involve narrowing the claims by introducing elements or limitations which are not supported by the as-filed disclosure is a violation of the written description requirement of 35 U.S.C. 112, first paragraph. See MPEP 2163.05 (II). See also In re Smith, 458 F.2d 1389, 1395, 173 USPQ 679, 683 (CCPA 1972) (“Whatever may be the viability of an inductive-deductive approach to arriving at a claimed subgenus, it cannot be said that such a subgenus is necessarily described by a genus encompassing it and a species upon which it reads.”). Thus the new limitation of amended claim 1 is new matter because it is not supported by the as-filed disclosure.
Claims 2, 3, and 7-11 are also rejected because these claims encompass new matter encompassed by the rejected claim above.
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.
Claims 1 and 3 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tsukamoto (Tsukamoto et al., US 2020/0383981 A1, Publication Date: 12/10/2020).
Since the specification does not define the term “removing suppression of anti-tumor immunity caused by a tumor cell”, given BRI, any anti-tumor activity would be considered as removing suppression of anti-tumor immunity caused by a tumor cell.
Tsukamoto teaches knockdown of Slug gene expression by shRNA, by introducing shRNA into MCA205 actAhR (Example 5, [0205]).
Tsukamoto teaches that Slug shRNA down-regulated Slug gene expression in mouse with activated AhR (Fig. 11 and [0207]).
Tsukamoto teaches that MCA205 actAhR NonTarget formed a tumor that was significantly larger than the mock. On the other hand, MCA205 actAhR shSlug, in which Slug gene expression was stably knocked down, formed small tumors equivalent to the mock. This indicates that tumor growth can be inhibited by suppressing the Slug gene. See Fig. 12 and [0213].
Tsukamoto teaches that MCA205 actAhR shSlug in which Slug gene expression was stably knocked down, IFN-γ production by cytotoxic T cells was significantly increased, indicating that anti-tumor immunity was enhanced (See Fig. 13 and [0215]). IFN-γ production is an indicator of anti-tumor immune activity by cytotoxic T cells (see [0177]).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 2, and 7-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tsukamoto (Tsukamoto et al., US 2020/0383981 A1, Publication Date: 12/10/2020), as applied to claims 1 and 3 above.
Regarding claims 2 and 8-11, Tsukamoto teaches as set forth above. However, Tsukamoto does not explicitly teach that wherein in the tumor cell a tyrosine residue(s) at the 111-th position and/or the 249-th position of human IDO1, or a tyrosine residue(s) of non-human IDO1 at a position(s) corresponding to the 111-th position and/or the 249-th position of human IDO1 is/are phosphorylated.
Tsukamoto teaches human IDO1 YYFF mutants which has Y111F and Y249F mutations ([0217]).
Tsukamoto teaches that human wild-type IDO1 induced high Slug gene expression but IDO1 YYFF mutant could not (Fig. 14, [0223] and Example 6).
Tsukamoto teaches mouse IDO1 YYFF mutant which has Y115F and Y253F mutations. Wild-type IDO1 induced high Slug gene expression but IDO1 YYFF mutant could not ([0045] and Fig. 6).
As shown below with an alignment of mouse and human IDO1, tyrosine-115 and tyrosine-253 residues of mouse IDO1 correspond to the 111-th position and/or the 249-th position of human IDO1:
indoleamine 2,3-dioxygenase 1 [Homo sapiens]
Sequence ID: NP_002155.1Length: 403Number of Matches: 1
Query 10 EGSRRILEDHHIDEDVGFALPHPLVELPDAYSPWVLVARNLPVLIENGQLREEVEKLPTL 69
E S I +++HIDE+VGFALP+P LPD Y+ W+ +A++LP LIE+GQLRE VEKL L
Sbjct 6 ENSWTISKEYHIDEEVGFALPNPQENLPDFYNDWMFIAKHLPDLIESGQLRERVEKLNML 65
Query 70 STDGLRGHRLQRLAHLALGYITMAYVWNRGDDDVRKVLPRNIAVPYCELSEKLGLPPILS 129
S D L H+ QRLA L LG ITMAYVW +G DVRKVLPRNIAVPYC+LS+KL LPPIL
Sbjct 66 SIDHLTDHKSQRLARLVLGCITMAYVWGKGHGDVRKVLPRNIAVPYCQLSKKLELPPILV 125
Query 130 YADCVLANWKKKDPNGPMTYENMDILFSFPGGDCDKGFFLVSLLVEIAASPAIKAIPTVS 189
YADCVLANWKKKDPN P+TYENMD+LFSF GDC KGFFLVSLLVEIAA+ AIK IPTV
Sbjct 126 YADCVLANWKKKDPNKPLTYENMDVLFSFRDGDCSKGFFLVSLLVEIAAASAIKVIPTVF 185
Query 190 SAVERQDLKALEKALHDIATSLEKAKEIFKRMRDFVDPDTFFHVLRIYLSGWKCSSKLPE 249
A++ Q+ L KAL +IA+ LEKA ++F ++ D V+P FF VLRIYLSGWK + +L +
Sbjct 186 KAMQMQERDTLLKALLEIASCLEKALQVFHQIHDHVNPKAFFSVLRIYLSGWKGNPQLSD 245
Query 250 GLLYEGVWDTPKMFSGGSAGQSSIFQSLDVLLGIKHEAGKESPAEFLQEMREYMPPAHRN 309
GL+YEG W+ PK F+GGSAGQSS+FQ DVLLGI+ AG A+FLQ+MR YMPPAHRN
Sbjct 246 GLVYEGFWEDPKEFAGGSAGQSSVFQCFDVLLGIQQTAGGGHAAQFLQDMRRYMPPAHRN 305
Query 310 FLFFLESAPPVREFVISRHNEDLTKAYNECVNGLVSVRKFHLAIVDTYIMKPSKKKPTDG 369
FL LES P VREFV+S+ + L +AY+ CV LVS+R +HL IV YI+ P+ ++P +
Sbjct 306 FLCSLESNPSVREFVLSKGDAGLREAYDACVKALVSLRSYHLQIVTKYILIPASQQPKEN 365
Query 370 DKSEEPSNVESRGTGGTNPMTFLRSVKDTTEKALL 404
SE+PS +E++GTGGT+ M FL++V+ TTEK+LL
Sbjct 366 KTSEDPSKLEAKGTGGTDLMNFLKTVRSTTEKSLL 400
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to use an shRNA to down-regulate Slug gene expression to treat cancer (e.g. removing suppression of anti-tumor immunity caused by a tumor cell), as taught by Tsukamoto, and to treat tumor, wherein in the tumor cell a tyrosine residue(s) at the 111-th position and/or the 249-th position of human IDO1, or a tyrosine residue(s) of non-human IDO1 at a position(s) corresponding to the 111-th position and/or the 249-th position of human IDO1 is/are phosphorylated, because Tsukamoto also teaches that phosphorylation at the 111-th position and/or the 249-th position of human IDO1, or a tyrosine residue(s) of non-human IDO1 at a position(s) corresponding to the 111-th position and/or the 249-th position of human IDO1 are required for induction of Slug gene expression. Thus, one of ordinary skill in the art would have recognized that a tumor with IDO1 phosphorylation at claimed position(s) would be more likely have higher Slug expression and be suitable for treatment by shRNA to Slug gene. Since the treatment is well known in the art as evidenced by Tsukamoto, one of ordinary skill in the art would have had a reasonable expectation of success to reach the claimed method. The motivation would have been to identify a suitable population for the claimed method.
Regarding claim 7, Tsukamoto teaches as set forth above. Additionally, , Tsukamoto teaches at paragraphs [0035-0037]: A method for screening a candidate substance for inhibiting expression of Slug gene or inhibiting synthesis of Slug, wherein the method includes: ex vivo measuring Slug inhibition activity by a test substance, inhibition activity against a factor which activates Slug by a test substance, expression of Slug gene by a test substance, or synthesis of Slug by a test substance, in a cell in which a tyrosine residue(s) at the 111-th position and/or the 249-th position of human IDO1, or a tyrosine residue(s) of non-human IDO1 at a position(s) corresponding to the 111-th position and/or the 249-th position of human IDO1 is/are phosphorylated, and/or in a cell in which AhR is activated; and selecting the candidate substance based on the measured Slug inhibition activity by the test substance, the inhibition activity against a factor which activates Slug by the test substance, measured expression inhibition of Slug gene by the test substance, or measured synthesis inhibition of Slug by the test substance.
Thus, it would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to target Slug gene for treating tumors, to use shRNA to suppress Slug gene expression as taught by Tsukamoto, and to further screen a more effective substance as claimed, because searching for a more effective substance that suppresses tumor invasion and metastasis was a well-known problem for an ordinary skill in the art. In order to obtain an inhibitory substance for Slug that is more effective than shRNA, a person skilled in the art would have easily conceived of screening for a substance that inhibits the expression and function of AhR and Slug by allowing a new candidate substance different from shRNA to act on the tumor cells in which the expression of AhR and Slug described in Tsukamoto. Given that Tsukamoto teaches the method of measuring Slug, one of ordinary skill would have had a reasonable expectation of success to reach the claimed invention. The motivation would have been to expand the options and to develop a more effective treatment.
Conclusion
No claims are allowed.
All other rejections set forth in the previous Office Action of December 23, 2024 are hereby withdrawn in view of the amendments and Applicants’ argument.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHENG LU whose telephone number is (571)272-0334. The examiner can normally be reached Monday-Friday 8-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571)270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHENG LU/ Examiner, Art Unit 1642
/PETER J REDDIG/ Primary Examiner, Art Unit 1646