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 .
Claim Status
Claims 1-33, 35-95, and 97-104 have been cancelled; claims 34 and 96 have been amended; and claims 105-111 have been newly added, as requested in the amendment filed on 07/21/2026. Following the amendment, claims 34, 96, and 105-111 are pending in the instant application.
Claims 34, 96, and 105-111 are under examination in the instant office action.
Claim Rejections - 35 USC § 103 - Withdrawn
Claims 34, 96, and 104 were rejected under 35 U.S.C. 103 as being unpatentable over WO 2018/100535 A1 (previously cited on PTO-892; herein after referred to as "Barbash") in view of non-patent literature by Frederick H. Wilson (Mol. Cancer Ther., 2017, 16, Abstract IA24; previously cited on PTO-892; herein after referred to as "Wilson") and non-patent literature by Barbarino et. al. (J. Cell. Mol. Med., Published Online 04/17/2020, 24, 5565-5577; previously cited on PTO-892; herein after referred to as "Barbarino").
It is noted that claim 104 has been canceled, rendering its rejection moot. Additionally, Applicant has amended independent claim 34 such that the claim is now limited to a method for suppressing growth of a melanoma having an MTAP deletion, comprising administering to a subject, generally, (i) a therapeutically effective amount of a PRMT5 inhibitor, wherein the PRMT5 inhibitor is a shRNA capable of decreasing expression of a PRMT5 protein by at least 10% and (ii) a therapeutically effective amount of an anti-PD1 antibody or antigen binding fragment thereof.
Applicant’s arguments, see Pages 5-9 of Remarks, filed 07/21/2026, with respect to the above-listed claim rejection under 35 USC § 103, particularly with respect to synergistic effects, have been fully considered and, in view of the instant claim amendments, are deemed persuasive. The rejection of claims 34, 96, and 104 were rejected under 35 U.S.C. 103 been withdrawn.
Art-Free Subject Matter
Upon further searching, it is noted that the closest prior art reference is US 2018/0271891 A1 (herein after referred to as “Garraway”). Garraway teaches therapeutic inhibition of PRMT5, and methods of identifying and treating PRMT5-related diseases in subjects or tissues which have an MTAP deficiency, alone or in combination, with a second agent that reduces MTAP activity and/or increases intracellular MTA levels, and/or provides MTA analogues to the cell or tissue (Abstract). Garraway further teaches that MTAP is deleted in 40% of glioblastomas; 25% of melanomas, urothelial carcinomas, and pancreatic adenocarcinomas; and 15% of non-small cell lung carcinomas (NSCLC) (Paragraph 0062), wherein melanoma is an exemplary cancer that may be treated by methods of Garraway (Paragraph 0168). Garraway teaches that pharmaceutical compositions (e.g., compositions comprising PRMT5 inhibitors) can also be administered in further combination with another agent, including any suitable therapeutic treatment for a particular cancer wherein exemplary additional agents include, for example, anti-PD1 antibodies (e.g., pembrolizumab and nivolumab) (Paragraphs 0264-0265). Garraway further teaches shRNAs targeting PRMT5 and WDR77, wherein it was observed that MTAP− lines (n=3447) were generally more sensitive to PRMT5 or WDR77 suppression (Paragraph 0276). While Garraway teaches/suggests methods of treating MTAP-deleted cancers (e.g., melanoma) with PRMT5 inhibitors (e.g., shRNA) in combination with other agents (e.g., anti-PD1 antibodies). However, it is specifically noted that Garraway does not teach or suggest that a combination therapy according to the instant claims would yield synergistic effects. As such, in view of secondary considerations, the instant claims are considered to be free of the prior art.
However, as amended, the instant claims suffer from deficiencies under 35 USC § 112 as detailed below.
Claim Rejections - 35 USC § 112 - New, as Necessitated by Amendment
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 34, 96, and 105-111 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. This is a WRITTEN DESCRIPTION rejection.
Independent claims 34 and 108, and subsequently dependent claims 96, 105-107, and 109-111, are generally drawn methods for suppressing tumor growth of a melanoma having an MTAP deletion comprising administering: (i) a therapeutically effective amount of a PRMT5 inhibitor, wherein the PRMT5 inhibitor is a short hairpin RNA (shRNA) and is capable of decreasing expression of a PRMT5 protein by at least 10%, and (ii) a therapeutically effective amount of an anti-PD1 antibody or antigen binding fragment thereof.
Thus, the claims identify the PRMT5 shRNA by the function of decreasing expression of a PRMT5 protein by at least 10%; the claims do not provide any specific structural feature of the shRNA that corresponds to the claimed function. Thus, the claims encompass a vast genus of PRMT5 inhibitors that are a shRNA and are required to decrease expression of a PRMT5 protein by at least 10%.
The instant specification discloses two species PRMT5 inhibitors that are shRNAs: shPRMT5-1 (TRCN0000181891) and shPRMT5-1 (TRCN00001182569), which hybridize to the PRMT5 gene. The shRNAs were combined, transduced into B16F10 cells, and then mice were inoculated with the transduced B16F10 cells to test their ability to inhibit tumors (see Example 3, Figures 5A-L).
Thus, the instant specification discloses making two species PRMT5 inhibitors that are shRNAs: shPRMT5-1 (TRCN0000181891) and shPRMT5-1 (TRCN00001182569), which hybridize to the PRMT5 gene and are capable of reducing PRMT5 protein expression as instantly claimed. The specification fails to disclose any other shRNAs that possess the function to decrease expression of a PRMT5 protein by at least 10%.
To provide adequate written description and evidence of possession of the claimed shRNA genus, the instant specification can structurally describe representative shRNAs that function to reduce expression of a PRMT5 protein by at least 10%, or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.).
In this case, the only factor present in the claims is a recitation of the shRNA function, “decreasing expression of a PRMT5 protein”. The instant specification fails to describe structural features common to the members of the shRNA genus, which features constitute a substantial portion of the genus because the instant specification fails to disclose a sufficient number of representative shRNAs that function as claimed. A definition by function does not suffice to define the genus because it is only an indication of what the shRNA does, rather than what it is. Other than for the shRNAs disclosed in Example 3, the specification fails to provide structural features coupled to the claimed functional characteristics. The instant specification fails to describe a representative number of shRNA sequences for the genus of shRNAs that function as claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed shRNA genus required to perform the claimed methods.
Although Applicants may argue that it is possible to screen for shRNAs that function as claimed, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘requires a precise definition, such as by structure, formula, chemical name, or physical properties,’ not a mere wish or plan for obtaining the claimed chemical invention.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future shRNAs yet to be discovered that may function as claimed.
Given the lack of representative examples to support the full scope of the claimed shRNAs, and lack of reasonable structure-function correlation with regards to the shRNAs that provide the function of decreasing PRMT5 protein expression, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of shRNAs that function to decrease expression of a PRMT5 protein as required to practice the claimed methods.
Examiner Suggestion: Examiner suggests amending the claims such that they require the shRNA to be complementary to or hybridize to PRMT5 mRNA.
Conclusion
Claims 34, 96, and 105-111 are pending. Claims 34, 96, and 105-111 are rejected. No claims are allowed.
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 ALYSSA RAE STONEBRAKER whose telephone number is (571)270-0863. The examiner can normally be reached Monday-Thursday 7:00 am - 5:00 pm.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALYSSA RAE STONEBRAKER/Examiner, Art Unit 1642
/Laura B Goddard/Primary Examiner, Art Unit 1642
