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 without traverse of Group III, claims 38-41 and 44, drawn to a pharmaceutical composition for treating liver cancer and a method of its use in treatment; and the species of nucleic acid, SMARCA4 and IRAK1, and Gankyrin in the reply filed on 22 September 2025 is acknowledged. Claims 25-44 are pending. Claims 21-27 and 42-43; and the species SMARCCI and SMARCA2 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. According claims 38-41 and 44 are pending and being examined on the merits.
Priority
This application is a 371 PCT of KR2021/009313 filed 07/20/2021. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. 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.
Information Disclosure Statement
The information disclosure statement filed 1/19/2023 has been considered.
Drawings
The drawings are objected to because there are different figure numbers on the same sheet. It would be remedial to place Fig. 3A and 6A on a separate sheet. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on page 26 and Figure 1a. 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.
The use of the terms Invivofectamine, Turbofect, and Encode, to name a few, which is either a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. Please check the disclosure for other marks or names.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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 38-41 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.
MPEP 2163.II.A.3.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. “Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date.” See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014).”
Claim 38 is directed to a “A pharmaceutical composition for preventing or treating liver cancer comprising a SMARCA4 inhibitor as an active ingredient”. Possession of these claims requires the possession of all structures capable of functioning as SMARCA4 inhibitors. Additionally, possession of these claims require the possession of all SMARCA4 inhibitors capable of preventing or treating liver cancer.
The current specification, as filed, discloses that the SMARCA4 inhibitor may be siRNA [pg. 14, line 24; example 2]. The specification does not disclose any other structure that is capable of functioning as a SMARCA4 inhibitor or any other SMARCA4 inhibitor that is capable of preventing or treating liver cancer.
Regarding genetic inhibitors of protein expression, Smith (Smith et al. PLoS Biol. 2017 Nov 30;15(11):e200321) analyses types of genetic perturbations, RNAi and CRISPR, in which both are used to generate loss-of-function [author summary]. Smith teaches that the off-target effects of RNAi are much greater than typically appreciated, whereas CRISPR technology has negligible off-target activity [author summary]. Smith further teaches that that the RNAi machinery includes the use of either siRNAs or shRNAs [pg. 2, para 3]. Xue (Xue et al. Nat Commun. 2019 Feb 4;10:557) teaches using a shSMARCA4 to knockdown SMARCA4 generating cells with a loss of SMARCA4 function.
Therefore considering the large variation of gene inhibitors that lead to protein loss of function; the failure of the specification to describe multiple SMARCA4 inhibitor or a common structure of the inhibitors; the failure of the specification to describe or provide predictability for preventing or treating all cancers using each SMARCA4 inhibitor; and the lack of predictability provided by the art for the full scope of the claimed genus, it is reasonable to conclude that Applicant did not possess the invention as claimed at the time of filing.
The additional dependent claims do not further limit the genus of inhibitor so as to resolve the issues above, and are therefore not sufficiently described for at least the reasons above.
Claim Rejections - 35 USC § 102
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.
Claim 38 and 41 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen (Chen et al. Cell Death and Disease (2018) 9:59).
Regarding claims 38 and 41, Chen teaches that BRG1 (i.e., SMARCA4) is upregulated in hepatocellular carcinoma (HCC), is higher in HCC tissues than in normal liver tissues, and may be involved in HCC progression [pg. 3, col. 1, para 2 – col. 2, para 2]. Chen teaches that that disruption of BRG1 gene expression inhibited proliferation of HCC cells and significantly reduced tumour size and weight [pg. 3, col. 2, para 3; Fig. 3]. Chen teaches that knockdown of BRG1 expression, using a lentiviral shRNA, was observed to not only arrest the cell cycle at G1/S but also to promote apoptosis of HCC cells [pg. 4, col. 1, para 1; Fig. 3; pg. 10, col. 2, para 2]. Claims 38 and 41 are drawn to a product, not a method of using the product. Therefore the recitation “for preventing or treating liver cancer” and “wherein the liver cancer is hepatocellular carcinoma” is an intended use of the product.
Claim Rejections - 35 USC § 103
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 38, 41 and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Chen (Chen et al. Cell Death and Disease (2018) 9:59).
Regarding claims 38, 41 and 44, Chen teaches that BRG1 (i.e., SMARCA4) is upregulated in hepatocellular carcinoma (HCC), is higher in HCC tissues than in normal liver tissues, and may be involved in HCC progression [pg. 3, col. 1, para 2 – col. 2, para 2]. Chen teaches that that disruption of BRG1 gene expression inhibited proliferation of HCC cells and significantly reduced tumour size and weight [pg. 3, col. 2, para 3; Fig. 3]. Chen teaches that knockdown of BRG1 expression was observed to not only arrest the cell cycle at G1/S but also to promote apoptosis of HCC cells [pg. 4, col. 1, para 1; Fig. 3].
It would be obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to use a pharmaceutical composition comprising a SMARCA4 inhibitor as an active ingredient in a method for preventing or treating hepatocellular carcinoma liver cancer. One of ordinary skill would be motivated to use the inhibitor in this method given Chen’s teaching that disruption of BRG1 gene expression inhibited proliferation of HCC cells, significantly reduced tumour size and weight, arrest the cell cycle at G1/S and promoted apoptosis of HCC cells.
Claims 39-40 are rejected under 35 U.S.C. 103 as being unpatentable over Chen (Chen et al. Cell Death and Disease (2018) 9:59) as applied to claim 38 and further in view of Zhi-hua (Zhi-hua et al. OncoTargets and Therapy 2017:10 1711–1723).
The teachings of Chen are discussed above as applied to claim 38 and similarly apply to claims 39-40.
Chen does not teach or suggest where the pharmaceutical composition further comprises an or an IRAK1 inhibitor or where IRAK1 is overexpressed in the liver cancer.
Zhi-hua teaches that IRAK1 is upregulated (i.e. overexpressed) in HCC tissues and that IRAK1 exhibited a significant diagnostic value for HCC [abstract]. Zhi-hua teaches that IRAK1 expression was observed to be associated with tumor size, metastasis and T-stage and that the upregulation of IRAK1 predicted a worse overall survival of HCC [abstract]. Zhi-hua teaches that IRAK1 may augment the malignant potential of HCC by stimulating the proliferation of cells and suppressing the apoptosis of cells [pg. 1717, col.1 - col.2 under ‘Discussion’].
It would be obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to additionally include an IRAK1 inhibitor in the pharmaceutical composition as taught and suggested by Chen for use in HCC which has an upregulation of IRAK1 as taught by Zhi-hua. One of ordinaty skill would be motivated to make the modification for the advantage of eliminating HCC’s tumor cells and size, metastasis and T-stage given’s Zhi-hua’s teaching that IRAK1 expression was observed to be associated with tumor size, metastasis and T-stage.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY N GROOMS whose telephone number is (571)272-3771. The examiner can normally be reached M-F 830-530.
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/TIFFANY NICOLE GROOMS/Examiner, Art Unit 1637