DETAILED ACTION
Claims 66-93, submitted on 28 July 2026, are pending in the application and subject to examination in the instant Office 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 the species of Formula (I),
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and the disclosed species of prostate cancer in the reply filed on 28 July 2026 is acknowledged.
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 66-93 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for cancer types that explicitly harbor PRC2 complexes with EZH2 mutations (e.g., metastatic diffuse large B-cell lymphoma cell line which expresses the mutant EZH2 enzyme), does not reasonably provide enablement for all cancer types. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Breadth of the Claims
Instant claim 66 recites “A method for treating cancer…”. The instant claim is not drawn to any cancer in particular and thus can be interpreted to encompass all known types of cancer. Additionally, “treatment” is broadly defined by Applicant in paragraph [0072] to mean “any manner in which the symptoms or pathology of a condition, disorder, or disease in a patient are ameliorated or otherwise beneficially altered.” “Therapeutically effective amount” is also broadly defined in paragraph [0071] as, “an amount that is sufficient to ameliorate or in some manner reduce a symptom or stop or reverse progression of a condition, or negatively modulate or inhibit the activity of PRC2 complex.”
Nature of the Invention
The nature of the invention is within the pharmaceutical arts with regards to treating a cancer in a patient by administering an effective amount of a compound of Formula (I).
State of the Prior Art
The state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains. The relative skill of those in the art refers to the skill of those in the art at the time the application was filed. See MPEP 2164.05(b). See Pac. Bioscience of Cal., Inc.
v. Oxford Nanopore Techs., Inc., 996 F.3d 1342, 1352, 2021 USPQ2d 519 (Fed. Cir. 2021).
The state of the prior art provides evidence for the degree of predictability in the
art and is related to the amount of direction or guidance needed in the specification as
filed to meet the enablement requirement. The state of the prior art is also related to the
need for working examples in the specification. See MPEP 2165.05(a).
Bradley et al. ("EZH2 inhibitor efficacy in non-Hodgkin’s lymphoma does not require suppression of H3K27 monomethylation." Chemistry & biology 21.11 (2014): 1463-1475.) teaches that “EZH2 is prevalently overexpressed in many cancer types including breast and prostate cancer, in which EZH2 level elevation correlates with the stage of the disease and poor prognosis” (pg. 1463, Section “Introduction”, Right Col., 2nd paragraph). Along with the overexpression in cancers such as breast cancer and prostate cancer, Bradley also states that “Our data suggest that NHL cells are indeed dependent on the catalytic activity of EZH2…” (pg. 1464, Section “Introduction”, Left Col., 2nd paragraph).
The current invention is drawn to the inhibition of PCR2 complexes containing EZH2 activating mutations. However, loss of function EZH2 mutations are also known in the art to contribute to certain types of cancers. Kim ("Targeting EZH2 in cancer." Nature medicine 22.2 (2016): 128-134.) teaches that “Recurrent inactivating deletion, frameshift, nonsense and missense mutations in EZH2 occur in a subset of myelodysplastic syndromes (MDS), myeloproliferative neo plasms (MPN) and MDS-MPN overlap disorders” (pg. 132, Section “Loss-of-function EZH2 mutations in cancer”, Left Col., 1st paragraph). This reference also teaches that human T cell acute lymphoblastic leukemia also occurs in loss-of-function mutations and deletions of EZH2 (pg. 132, Section “Loss-of-function EZH2 mutations in cancer”, Left Col., 2nd paragraph). In view of the teachings of Kim, there is unpredictability in the treatment of cancers which exhibit a loss of function mutation of EZH2 through administration of a compound which would inhibit cells harboring PRC2 complexes containing EZH2 activating mutations.
Level of Skill in the Art
The person of ordinary skill in the art is a person who is presumed to have known the relevant art at the relevant time. Factors that may be considered in determining the level of ordinary skill in the art may include: (A) “type of problems encountered in the art;” (B) “prior art solutions to those problems;” (C) “rapidity with which innovations are made;” (D) “sophistication of the technology; and” I “educational level of active workers in the field. In a given case, every factor may not be present, and one or more factors may predominate.” In re GPAC, 57 F.3d 1573, 1579, 35 USPQ2d 1116, 1121 (Fed. Cir. 1995); Custom Accessories, Inc. v. Jeffrey-Allan Indus., Inc., 807 F.2d 955, 962, 1 USPQ2d 1196, 1201 (Fed. Cir. 1986); Environmental Designs, Ltd. V. Union Oil Co., 713 F.2d 693, 696, 218 USPQ 865, 868 (Fed. Cir. 1983). See MPEP 2141.03 (I).
The invention described pertains to the medical or pharmaceutical arts. One of ordinary skill would be trained in pharmacology, biochemistry, medicine, or a related art with a Ph. D or other advanced degree in these or other related fields.
Level of Predictability in the Art
The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability of the art. In re Fisher, 427, F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art in unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling.
The scope of the required enablement varies inversely with the degree of predictability involved, but even in unpredictable art, a disclosure of every operable species is not required. A single embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements. In re Vickers, 141 F.2d 522, 526-27, 61 USPQ 122, 127 (CCPA 1944); In re Cook, 439 F.2d 730, 734, 169 USPQ 298, 301 (CCPA 1971). However, in applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). See MPEP 2164.03. The applicant would need to provide more objective evidence to support the enablement of the aforementioned claims to contrast the unpredictability of the subject matter art.
There is unpredictability in the field of endeavor regarding the currently claimed method of treating all cancers with a single compound. The unpredictability is based on the fact that not all cancers that contain PCR2 complexes exhibit the EZH2 activating mutations, as described above in section (C).
Amount of Direction Provided by the Inventor
The amount of direction provided by the inventor is correlated by the nature of the unpredictability of the art. Given the context and scope of the claims mentioned above, the inventor failed to provide the necessary amount of direction for one skilled in the art to adequately use the invention across all suggested utility in the broadly stated disease and disorders disclosed above. (See: Section (A) Breadth of the Claims).
The Applicant provided guidance with respect to the synthesis of the compounds of Formula (I), found in Examples 1-45 on pages 88-133 of the instant specification. Example A, found on pages 133-135 of the specification, discloses the claimed compounds ability to inhibit PCR2-mediated enzymatic activity. Examples B and C also disclose the inhibitory effects of the claimed compounds on two lymphoma cells lines. Example B uses the Pfeiffer cell line which contains PCR2 complexes with EZH2 activating mutations and Example C uses the Karpas 422 cell line which also contains EZH2 mutations which increase histone H3 methylation.
Existence of Working Examples
The provided working examples focused on the inhibitory effects of the compounds on PCR2 complexes with EZH2 activating mutations in two lymphoma cell lines. The prior art was relied upon to support the claim limitations in which the cancers are breast cancer and prostate cancers, particularly wherein the Bradley reference teaches that elevated levels of EZH2 correlates with the stage of the disease and poor prognosis. The specification and prior art do not, however, support the notion that the compounds of the instant invention would be effective in treating all cancers. Thus, one skilled in the art would be unable to adequately use the invention without unduly experimentation, which would require the practitioner to discover that which the Applicant has failed to disclose.
Quantity of Experimentation Needed to Make or Use the Invention Based on the Content of the Disclosure
As previously stated, the amount of experimentation depends on the art, the predictability of the art, and the direction provided by the inventor. For one skilled in the art to practice the invention as disclosed, the applicant would be required, but not limited
to providing:
Experimentation to show treatment of all claimed forms of cancer as claimed in instant claim 1.
Experimentation to show dosage and frequency required in the treatment of all claimed cancers.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 66-91 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 12,252,493. Although the claims at issue are not identical, they are not patentably distinct from each other because independent claim 1 of USPN ‘493 is drawn to a genus that renders obvious the instantly rejected claims. Independent claim 1 of USPN ‘493 claims a compound of Formula (I) (shown below), which is identical to that of the genus recited by the Applicant in the instantly rejected claims. While the aforementioned claims of USPN ‘493 and of the instantly claimed invention pertain to different statutory categories, and as USPN ‘493 does not recite the intended use of the compound, the Examiner notes that the invention as defined in the specification of USPN ‘493 recites “The compositions and methods provided herein may be used for the treatment of a wide variety of cancer including tumors such as prostate, breast, brain, skin, cervical carcinomas, testicular carcinomas, etc.” (Col. 27, Lines 22-25). Consequently, it is proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010). As such, the disclosure of USPN ‘493 teaches an identical utility, thus obviating that of the instant application which necessitates the instant rejection.
Genus taught by USPN ‘493
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(Col. 154, Lines 5-20)
Genus taught by Applicant in claim 66
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The aforementioned claim of USPN ‘493 obviates instant claim 66 because the genus taught by USPN ‘493 is identical to that of the Applicant.
Claims 2-25 of USPN ‘493 also recite identical limitations to that of instant claims 67-90 of the instant application resulting in identical compounds being claimed in claim 26 of USPN ‘493 and claim 91 of the instant application. Therefore, the claims of USPN ‘493 clearly obviate the claims of the instant application.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JUSTIN CHRISTOPHER SANCHEZ whose telephone number is (703)756-5336. The examiner can normally be reached Monday -Friday (0730-1700).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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JUSTIN CHRISTOPHER SANCHEZ
Examiner
Art Unit 1622
/J.C.S./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
Prosecution Insights