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 .
Application Status
Applicant’s remarks, and amendments to the claims, drawings, and specification filed June 2, 2026 are acknowledged. Claims 1 and 3 were amended, and claims 6-10, and 12-14 were cancelled. Claims 1-5, 11, and 15-20 are pending.
Restriction/Election
Claims 15-20 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1-5, and 11 are under examination hereinafter.
Withdrawn Rejections
Applicant’s remarks and amendments to the claims have been thoroughly reviewed. The amendments to claim 1 to require that the method be for treating “Ras mutant acute myeloid leukemia (AML) in a subject in need thereof” are sufficient to overcome the § 103 rejections raised in the prior action over Kharas, Becker, Tzelepis, and Ivanov, and the aforementioned in further view of GenBank, NM_005762.3 and Moore. The prior art suggests that Trim28 is a “druggable” “AML-specific” target (see Tzelepis, of record), and generally teaches that Ras mutations, and specifically, N-Ras and K-Ras mutations are associated with AML (see Bowen et al., 15 September 2005, Blood, Vol. 106, No. 6, pg. 2113-2119). However, neither the prior art cited in the previous action, nor the prior art reviewed in the updated search, teaches or suggests treating N-Ras or K-Ras mutant AML using a Trim28-specific inhibitory nucleic acid as demonstrated in the instant application. See at least Fig. 6, which shows that Trim28-specific inhibitory nucleic acids block proliferation of N-Ras and K-Ras mutant AML cells, and Example 3 and Fig. 5, which provides evidence that Trim28-specific inhibitory nucleic acids treat N-Ras mutant AML in vivo. The aforementioned rejections are withdrawn.
Applicant’s remarks and amendments have been thoroughly considered, but are not persuasive to place the claims in condition for allowance for the reasons that follow. Any rejection or objection not reiterated herein has been overcome by amendment.
Priority
Applicant's priority claims to Application Nos. 62/802,520 and PCT/US20/17049 are acknowledged. Claims 1-5, and 11 under examination find support in Application No. 62/802,520, and therefore, have an effective filing date of February 7, 2019.
Claim Objections
Claims 1 and 3 are objected to because of the following informalities:
Claim 1 recites “the at least one Trim28-specific inhibitory nucleic acid has a 20-22 base pair length sequence that is 100% complementarity to a coding region of a Trim28 nucleic acid sequence.” The claim should be amended to recite “that is 100% complementary
Claim 3 recites that “the at least one Trim28-specific inhibitory nucleic acid comprises a nucleic acid sequence selected from the group consisting of: … []SEQ ID NO: 1[]… []SEQ ID NO: 10[].” The sequence listing provides that the sequences set forth SEQ ID NOs: 1-10 are composed of “DNA” nucleotides. It is clear based on claim 1 that the Trim28-specific inhibitory nucleic acid must be an “shRNA or a sgRNA,” each of which are composed of RNA nucleotides. Claim 3 should be amended to recite the following, for example, accordingly: “wherein the at least one Trim28-specific inhibitory nucleic acid comprises a nucleic acid sequence 100% identical to a nucleic acid sequence selected from the group consisting of: … []SEQ ID NO: 1[]… []SEQ ID NO: 10[].”
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-5, and 11 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The rejections that follow are maintained and modified as necessitated by Applicant’s amendments to the claims.
Claim 1 recites “wherein the at least one Trim28-specific inhibitory nucleic acid is a shRNA or sgRNA… wherein the at least one Trim28-specific inhibitory nucleic acid has a 20-22 base pair length sequence that is 100% complementar[y] to a coding region of a Trim28 nucleic acid sequence.” The term “sgRNA” is interpreted as a “synthetic guide RNA,” which the specification provides comprises a crRNA segment complementary to the target sequence ([0071]). The skilled artisan would know that a crRNA segment is a single-stranded sequence, typically between 17-24 nucleotides in length, which is designed to base pair with a target sequence, but does not, itself, comprise “base pairs.” An “shRNA” does, in contrast, comprise a double-stranded region, typically between 19-25 base pairs in length, which comprises a sequence complementary to a target sequence ([0070]).
Claim 1 requires that the “at least one Trim28-specific inhibitory nucleic acid” comprise “a 20-22 base pair length sequence that is 100% complementar[y] to a coding region of a Trim28 nucleic acid sequence.” It is not clear how or if this limitation applies to a Trim28-specific inhibitory nucleic acid which is an sgRNA, given the apparent structural incompatibilities with the term sgRNA as it would be interpreted by one of ordinary skill. For example, it is not clear I) whether the phrase intends to further limit the sequence of the crRNA segment, such that it forms intramolecular base pairs, or II) whether the phrase “base pair length” refers to a function of the 20-22 nucleotide sequence, such that the sequence does not actually require base pairs but is capable of base pairing, or III) whether the phrase was intended to apply only to a Trim28-specific inhibitory nucleic acid which is an shRNA, which inherently comprises a double-stranded region complementary to a target sequence.
Claims 2-5, and 11 are rejected for depending from claim 1 and failing to remedy the indefiniteness.
Response to Remarks - 35 USC § 112(b)
Applicant’s remarks regarding the § 112(b) rejections raised in the prior action have been reviewed. The remarks are moot, because the substance of the remarks does not pertain to the maintained and modified rejections described above, which are necessitated by Applicant’s amendments to the claims.
Claim Rejections - 35 USC § 112(a) – Written Description
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 1-5, and 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. This is a new matter rejection necessitated by Applicant’s amendments to the claims.
MPEP 2163.03(I) provides that “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981).”
Claim 1 has been amended to recite a “method for treating Ras mutant acute myeloid leukemia (AML) in a subject in need thereof.” Applicant’s remarks indicate that support for the amendments to the claims are found in paragraphs [0066], [0070]-[0071], [0075], and Fig. 6 of the specification. Paragraphs [0066], [0070]-[0071], and [0075] pertain to features of the Trim28-specific inhibitory nucleic acid, and are not relevant to the aforementioned amendments to claim 1. Fig. 6 shows the results of constitutively expressing Cas9 and sgRNA targeting Trim28 in “thp1(MLL-AF9/Nras)” and “ml-2(MLL-AF6/KRAS)” cells. Fig. 6 provides description for treating N-Ras and K-Ras mutant acute myeloid leukemia (AML), but does not provide description for treating “Ras mutant acute myeloid leukemia (AML)” generally, which is interpreted as AML comprising any mutation in any Ras family member, including N-Ras, K-Ras, and H-Ras. The disclosure as a whole was reviewed. No description of treating Ras mutant AML in general was uncovered. The review uncovered description of subjects comprising “one or more point mutations in NRAS” ([0085]), but this specific description does not provide description for treating Ras mutant AML in general. Accordingly, the newly introduced limitations fail to comply with the written description requirement.
Claims 2-5, and 11 are rejected for encompassing new matter introduced to claim 1, and failing to remedy the written description issues therein.
Conclusion
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 JENNA L PERSONS whose telephone number is (703)756-1334. The examiner can normally be reached M-F: 9-5pm.
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, JENNIFER A DUNSTON can be reached at (571) 272-2916. 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.
/JENNA L PERSONS/Examiner, Art Unit 1637
/Soren Harward/Primary Examiner, TC 1600
Prosecution Insights