DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-3, 5, 7-10, 12, and 14-24 are pending. Claims 4, 6, 11, and 13 are cancelled.
Status of Priority
The present application is a 35 U.S.C. § 371 national stage patent application of International patent application PCT/US2023/021679, filed on May 10, 2023. This application also claims the benefits of priority to U.S. Provisional Application No. 63/364,454, filed on May 10, 2022.
Specification - Abstract
The abstract of the disclosure is objected to because it is not in compliance with 37 C.F.R. 1.72 (b). Specifically, the sheet presenting the abstract includes other parts of the application or other material. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Applicant is reminded of the proper content of an abstract of the disclosure.
In chemical patent abstracts for compounds or compositions, the general nature of the compound or composition should be given as well as its use, e.g., “The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics.” Exemplification of a species could be illustrative of members of the class.
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
Specification - Disclosure
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Examiner’s note on novelty and nonobviousness
The closest prior art is:
Schönbrunn et al. (Schönbrunn-2016) (WO2016022460A1; published February 11, 2016),
Schönbrunn et al. (Schönbrunn-2020) (WO2020051572A1; published March 12, 2020), and
Ember et al. (Ember) (Ember, S. W. et al. Potent Dual BET Bromodomain-Kinase Inhibitors as Value-Added Multitargeted Chemical Probes and Cancer Therapeutics. Mol Cancer Ther 2017, 16, 1054-1067.)in view of
Bhullar et al. (Bhullar) (Bhullar, K. S. et al. Kinase-targeted cancer therapies: progress, challenges and future directions. Mol Cancer 2018, 17, pg. 1-20.) and
Tauro et al. (Tauro) (Tauro, M. et al. Abstract PD3-10: Dual epigenetic/autophagy inhibition as a novel strategy to tackle triple negative breast cancer. Cancer Res 2022, 82, PD3-10.; available February 15, 2022.)
Novelty:
Novelty with respect to Schönbrunn-2016
Schönbrunn-2016 teaches potent dual BRD4 kinase inhibitors as cancer therapeutics (see abstract). One of the inhibitors disclosed in Schönbrunn-2016 is:
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(see Schönbrunn-2016, pg. 42, the compound in the table; note: this compound of Schönbrunn-2016 is the same as the compound of instant formula (I) recited in the instant claims). In addition, claim 40 of Schönbrunn-2016 recites a method of treating cancer in a subject comprising, administering to the subject an effective amount of a compound of any one of the preceding claims which encompasses the compound of instant formula (I). However, Schönbrunn-2016 generally teaches treatment of cancer without limiting the method to cancers associated with ULK3. Furthermore, Schönbrunn-2016 discloses the compound of instant formula (I) as a BRD4 kinase inhibitor (see abstract) and does not teach nor suggest that the therapeutic effect of the compound of instant formula (I) arises from inhibition of ULK3. Schönbrunn-2016 also does not identify or select cancers on the basis that they are ULK3-associated. In contrast, the instant claims are specifically directed to methods of treating ULK3-associated cancers, which is a distinct therapeutic application not disclosed in Schönbrunn-2016. Thus, the instant invention is considered novel with respect to Schönbrunn-2016.
Novelty with respect to Schönbrunn-2020
Schönbrunn-2020 teaches BRD4-JAK2 inhibitors (see abstract/title). One of the inhibitors disclosed in Schönbrunn-2020 is:
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(see Schönbrunn-2020, pg. 116, line 1; note: this compound of Schönbrunn-2020 is the same as the compound of instant formula (II) recited in the instant claims). In addition, claim 41 of Schönbrunn-2020 recites a method of treating cancer in a subject comprising, administering to the subject an effective amount of a compound or pharmaceutical composition of any one of the preceding claims which encompasses the compound of instant formula (II). However, Schönbrunn-2020 generally teaches treatment of cancer without limiting the method to cancers associated with ULK3. Furthermore, Schönbrunn-2020 discloses the compound of instant formula (II) as a BRD4-JAK2 inhibitor (see abstract/title) and does not teach nor suggest that the therapeutic effect of the compound of instant formula (II) arises from inhibition of ULK3. Schönbrunn-2020 also does not identify or select cancers on the basis that they are ULK3-associated. In contrast, the instant claims are specifically directed to methods of treating ULK3-associated cancers, which is a distinct therapeutic application not disclosed in Schönbrunn-2020. Thus, the instant invention is considered novel with respect to Schönbrunn-2020.
Nonobviousness:
Ember teaches compounds 3 and 5 which both have structures similar to those of the compounds represented by instant formulas (I) and (II):
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and
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(see Ember, Figure 1E). According to Ember, the “most significant differences in inhibitory potential were noted for ULK3, ULK1, and ERN2/IRE2, which were potently inhibited by compound 3 but appeared to be insensitive towards compound 5” (pg. 1059, left col., paragraph right below Figure 2, 2nd to last sentence). Thus, Ember itself demonstrates that structurally similar compounds within the same chemical series do not necessarily possess the same ULK3 inhibitory activity. Specifically, although compounds 3 and 5 are structurally related, compound 3 potently inhibited ULK3, whereas ULK3 appeared to be insensitive toward compound 5. Accordingly, Ember does not establish a predictable structure-activity relationship for ULK3 inhibition.
Moreover, even if a POSITA was motivated to prepare a compound structurally related to compounds 3 and 5 of Ember (such as the compounds of instant formulas I and II) and subsequently evaluate the compound for ULK3 inhibitory activity, successful inhibition of ULK3 would not, by itself, provide a reasonable expectation that such a compound would be therapeutically effective for treating a ULK3-associated cancer. According to Bhullar, generally, in the context of kinase-targeted cancer therapy, “[s]pecific tumor genetics, tumor microenvironment, drug resistance, and pharmacogenomics determine how useful a compound will be in the treatment of a given cancer” (see abstract, 2nd to last sentence). Thus, the therapeutic efficacy of a kinase inhibitor in a particular cancer also depends on factors beyond the compound’s biochemical ability to inhibit the kinase.
Furthermore, only a few months before the effective filing date of the instant invention, Tauro explicitly stated that “ULK3 has not been investigated to date in regulating TNBC cell intrinsic autophagy and no drugs exist that can inhibit ULK3” (see abstract – background, last sentence). Accordingly, as of that time, the prior art had not established a relationship demonstrating that pharmacological inhibition of ULK3 translated into treatment of a ULK3-associated cancer. Therefore, even if a POSITA found it obvious to prepare compounds structurally similar to compounds 3 and 5 of Ember (such as the compounds of instant formulas I and II) and subsequently evaluate such compounds for ULK3 inhibitory activity, the mere discovery that a compound inhibits ULK3 would not, by itself, have provided a reasonable expectation that the compound would also be therapeutically effective for treating a ULK3-associated cancer.
Thus, for at least the above reasons, the instant invention is considered nonobvious.
Claim Rejections - 35 USC § 112(a)
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.
Written Description
Claims 1, 8, 15-24 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.
According to MPEP § 2163:
“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, e.g., 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).
In the instant case, the specification does demonstrate possession of:
a method of treating a ULK3-associated cancer in a subject in need thereof, wherein the ULK3-associated cancer is multiple myeloma or breast cancer, the method comprising administering a therapeutically effective amount of a compound selected from the compound of instant formula (I) and (II), or a pharmaceutically acceptable salt thereof
The instant specification provides therapeutic efficacy data specifically for models of multiple myeloma and breast cancer (see the “Examples” section in the instant specification on pg. 32-33). However, the claims encompass methods of treating any ULK3-associated cancer. The instant specification does not disclose a representative number of methods of treating other ULK3-associated cancers spanning the breadth of the claimed genus, nor does it demonstrate that efficacy in multiple myeloma and breast cancer is representative of efficacy across the full scope of ULK3-associated cancers (or cancers, generally). Therefore, the instant specification fails to provide adequate written description support for the full scope of the claimed invention.
Moreover, the recitation of “ULK3-associated cancer,” without any limitation as to the cancers encompassed by that term creates a “reach-through” aspect to the claim. Specifically, the claim is not limited to cancers presently recognized as ULK3-associated cancer, but, instead, potentially reaches through to cancers whose relationship to ULK3 may only be discovered or established through future scientific investigation. In the instant case, the specification does not demonstrate possession of methods of treating cancers whose association with ULK3 was unknown or unrecognized at the time of filing, nor does it provide representative disclosure sufficient to show possession of such subsequently identified members of the claimed genus. Accordingly, the “reach-through” scope of the claim further demonstrates that the instant specification does not reasonably convey possession of the full scope of “ULK3-associated cancer” as presently claimed.
Furthermore, claim 19 recites, “the method of claim 1, wherein the compound is administered alone or in combination or alternation with one or more additional therapeutic agents.” Claim 20 further limits the additional therapeutic agent to an anticancer agent. However, the specification provides combination-therapy support only for administration of the claimed compounds with bortezomib or carfilzomib, which are both anticancer agents (for data pertaining to combination therapy with bortezomib: see Figs. 10A-10F and corresponding figure description in instant specification; for data pertaining to combination therapy with carfilzomib: see Figs. 11A-11E and corresponding figure description in instant specification).
Accordingly, the instant specification does not reasonably convey possession of the substantially broader genus encompassing administration of the claimed compounds with one or more additional therapeutic agents generally. The disclosure of a combination with bortezomib or carfilzomib does not demonstrate possession of combinations with therapeutic agents that are not anticancer agents. The written description therefore supports, at most, a limitation directed to administration of the claimed compound alone or in combination or alternation with one additional anticancer agent, rather than the broader recitation of “one or more additional therapeutic agents.”
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, 8, 15-24 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.
The limitation “ULK3-associated cancer” renders the scope of the claims indefinite because the claim defines the cancer only by its functional relationship to ULK3, without identifying which cancers are encompassed or providing an objective standard for determining when a cancer is sufficiently “associated” to ULK3 to fall within the scope of the claim. It is therefore unclear whether the limitation only encompasses cancers that were established to be directly driven by ULK3 activity as of the effective filing date, or does it also encompass cancers that may subsequently be discovered or later determined to involve ULK3 activity. It is further unclear whether the limitation encompasses cancers in which ULK3 activity contributes to pathogenesis directly or does the limitation encompass any cancer for which ULK3 produces some biological or therapeutic effect. Therefore, the limitation “ULK3-associated cancer,” renders the boundaries of the claimed genus to be vague and indefinite.
Allowable Subject Matter
Claims 2, 3, 5, 7, 9, 10, 12, and 14 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.
Conclusion
Claims 1, 8, and 15-24 are rejected. Claims 2, 3, 5, 7, 9, 10, 12, and 14 are objected to. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTEN ROMERO whose telephone number is (571)272-6478. The examiner can normally be reached M-F 9:30 AM - 6:00 PM ET.
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/KRISTEN W ROMERO/Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
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