CTNF 18/512,950 CTNF 86483 NON-FINAL REJECTION This application, filed Nov. 17, 2023, claims benefit of priority to Provisional Application 63/384,204, filed Nov. 17, 2022. Claims 1-24, as amended, are pending. Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Priority 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. Election/Restrictions Applicant’s election without traverse of Group I, drawn to compounds and compositions, and the compound species having the structural formula, PNG media_image1.png 316 512 media_image1.png Greyscale in the reply filed on May 21, 2026 is acknowledged. The elected compound reads on formula (Ib) as recited by claims 1-14, wherein: R1 is alkyl (methyl); R2 is substituted heteroaryl (pyridine substituted by chloro); R3 is substituted heteroaryl (1,3-benzodioxole di-substituted by fluoro); X2 is substituted trivalent heteroaryloxyl (1,3,5-triazine); Y2 is unsubstituted heterocyclyl (piperazine); L is a linker of formula -(CH 2 C(O)NH) m- (CH 2 ) 2 -(OCH 2 ) n -, where m is 0 and n is 3 (-CH 2 CH 2 O) 3 -CH 2 CH 2 -); and M E3 is PNG media_image2.png 206 338 media_image2.png Greyscale . Upon further consideration, the restriction/election requirement dated Mar. 2, 2026 is withdrawn. Claims 1-24 are currently pending and under consideration. Information Disclosure Statement The information disclosure statement (IDS) submitted on Jan. 17, 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner. Claim Rejections - 35 U.S.C. § 112(b) – Indefiniteness 07-30-02 AIA 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. 07-34-01 AIA 1. Claim 7 is 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 pre-AIA the applicant regards as the invention. Specifically, each claim must end with a period. See MPEP §608.01(m). 07-34-01 2. Claims 1-10 and 14-24 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. a. Specifically, claim 1 is drawn to compounds of formula (Ia) or (Ib), PNG media_image3.png 206 302 media_image3.png Greyscale or PNG media_image4.png 266 226 media_image4.png Greyscale , wherein "L is a bond or a linker." However, the specification fails to define the term "linker." While those skilled in the chemical arts generally understand the meaning of "linker" or "linking group," the term sets no particular limit on the functional groups, ring systems, or other chemical moieties which may link the two segments of the claimed compounds. Because the scope of the claimed compounds is undefined and open-ended, one of ordinary skill in the art would not be reasonably apprised of the scope of the claimed invention. Therefore, infringing compounds cannot be distinguished from non-infringing compounds, rendering the metes and bounds of the claims indefinite. b. Similarly, claim 1 defines M E3 as "a moiety that binds to an E3 ubiquitin ligase"; and claim 9 further limits this moiety to Von Hippel-Lindau (VHL) E3 ubiquitin ligase or cereblon (CRBN) E3 ubiquitin ligase. While the specification provides a few examples of these moieties (see, e.g., Fig. 1), these terms are nonetheless indefinite because they attempt to define a structural limitation in functional language. The instant specification fails to define "moiety that binds to an E3 ubiquitin ligase," "Von Hippel-Lindau (VHL) E3 ubiquitin ligase," and "cereblon (CRBN) E3 ubiquitin ligase," which also have no clear-cut, commonly understood structural definition. The exact set of substances encompassed by these terms, and excluded therefrom, cannot be ascertained by one of ordinary skill in the art. While methods of assaying for E3 ubiquitin ligase binding activity are known in the art, the term includes substances with levels of activity which are detectable but too low to have any therapeutic utility, as well as substances which have not yet been identified to have E3 ubiquitin ligase binding activity. As recognized by MPEP § 2173.05(g), a claim term is merely functional descriptive language when it recites a feature "by what it does rather than by what it is " (e.g., as evidenced by a specific structure). In re Swinehart , 439 F.2d 210, 212, 169 USPQ 226, 229 (CCPA 1971). Here, substances encompassed by the terms "linker" and "a moiety that binds to an E3 ubiquitin ligase" cannot be unambiguously distinguished from substances which are excluded. Therefore, infringing compounds cannot be distinguished from non-infringing compounds, rendering the metes and bounds of the claims indefinite. 07-34-01 3. Claims 15-16 is 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. Specifically, claim 15 is drawn to a method of treating " a disease or disorder associated with DOT1L activity in a subject in need thereof ," without a limiting definition of the diseases and/or disorders encompassed by this term. Similarly, claim 16 is drawn to a method of treating a disease or disorder which is " a cell proliferative disease or disorder ," without a limiting definition of the diseases and/or disorders encompassed by this term. The specification provides that "a subject in need of treatment" may include: a subject having a disease, disorder, or condition that is responsive to therapy with the compounds as disclosed herein. For example, a “subject in need of treatment” may include a subject having a cell proliferative disease, disorder, or condition such as cancer. In some embodiments, the cancer is a leukemia. In some embodiment, the leukemia is MLL-rearranged leukemia, such as acute myeloid leukemia (AML) or acute lymphoblastic leukemia (p. 29, lines 20-25). Thus, treatment of certain diseases and/or disorders are disclosed in the specification, e.g., leukemia, MLL-rearranged leukemia, acute myeloid leukemia, or acute lymphoblastic leukemia, as recited by claims 17-19. However, these are the only specific "diseases or disorders associated with DOT1L activity" and "cell proliferative diseases or disorders" disclosed. While one of ordinary skill in the art generally understands the terms "disease or disorder associated with DOT1L activity" and "cell proliferative disease or disorder," they are not defined in the specification, and are not art-recognized terms with clear-cut boundaries. For example, "cell proliferative diseases or disorders" can be benign or malignant, and can include, e.g., psoriasis, eczema, keloids, and lipomas, as well as, e.g., pancreatic cancer, glioblastoma, melanoma, and breast or prostate cancer. Thus, "cell proliferative diseases or disorders" encompass widely divergent diseases with different etiologies that would not be appropriately treated with or expected to respond to the same therapies. Because the specification fails to unambiguously define the claimed diseases and disorders, one of ordinary skill in the art would be unable to distinguish the patient population(s) which are encompassed by the claims, from those which are excluded. Therefore, infringing methods cannot be distinguished from non-infringing methods, rendering the metes and bounds of the claims indefinite. Claim Objections 12-151-08 AIA 07-43 12-51-08 Claim s 11-13 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Citation of Additional Prior Art Additional references made of record are considered pertinent to applicant's disclosure: WO 2020/006157, WO 2023/069348, and WO 2023/004283 (all cited on PTO-892). Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARA E. TOWNSLEY whose telephone number is 571-270-7672. The examiner can normally be reached on Mon-Fri from 10:00 am to 6:00 pm (EST). If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jeff S. Lundgren, can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://portal.uspto.gov/ external/portal. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). /SARA E. TOWNSLEY/Examiner, Art Unit 1629 Application/Control Number: 18/512,950 Page 2 Art Unit: 1629 Application/Control Number: 18/512,950 Page 3 Art Unit: 1629 Application/Control Number: 18/512,950 Page 4 Art Unit: 1629 Application/Control Number: 18/512,950 Page 5 Art Unit: 1629 Application/Control Number: 18/512,950 Page 6 Art Unit: 1629 Application/Control Number: 18/512,950 Page 7 Art Unit: 1629
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