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 .
DETAILED ACTION
Claims 1-4, 11, 14, 17, 21, 29, 33-37, 42-43, 45 and 47 are currently pending in the instant application. Applicants have amended claims 11, 14, 17, 21, 29 and 33-37 and canceled claims 5-10, 12-13, 15-16, 18-20, 22-28, 30, 31, 32, 38-41, 44 and 46 in an amendment filed on August 27, 2026. Claims 1, 17, 21, 29, 33, 34, 36, 42, 43, 45 and 47 are rejected, claims 2, 3, 4, 11, 14 and 37 are considered allowable and claim 35 is objected in this Office Action.
I. Priority
The instant application is a 371 of PCT/US2023/025576, filed on June 1, 2023.
II. Information Disclosure Statement
The information disclosure statements (IDS) submitted on December 13, 2024 and August 27, 2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
III. Rejections
35 USC § 103 - OBVIOUSNESS REJECTION
The following is a quotation of 35 U.S.C. § 103(a) that forms the basis for all
obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Graham v. John Deere Co. set forth the factual inquiries necessary to determine obviousness under 35 U.S.C. §103(a). See Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Specifically, the analysis must employ the following factual inquiries:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 17, 21, 29, 33, 34, 36, 42, 43, 45 and 47 are rejected under 35 U.S.C. § 103(a) as being unpatentable over Villemure, et al. (WO 2023/018648 A1). Applicants claim a compound of formula
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The Scope and Content of the Prior Art (MPEP §2141.01)
Villemure, et al. phenol naphthalene derivatives that inhibit the degradation of BRM. The invention is represented by the general formula:
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. And all other variables are as defined on pages 3-4 of the prior art reference. The prior art also teaches various species such as
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(see page 210, compound 5).
The Difference Between the Prior Art and the Claims (MPEP §2141.02)
The difference between the prior art of Villemure, et al. and the instant invention is that the prior art teaches various species such as
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that have been excluded in the proviso language found in the instant claims. However, the instant claimed invention includes similar compounds that have a methyl substitution on the pyridine ring (variable R6) instead of a hydrogen as seen in the prior art. Therefore, the difference between the prior art’s compounds and instant compounds would be a Me vs H.
Prima Facie Obviousness-The Rational and Motivation (MPEP §2142-2413)
Compounds that differ only by the presence or absence of an extra methyl group or two are homologues. Homologues are of such close structural similarity that the disclosure of a compound renders prima facie obvious its homologue. As was stated in In re Grose, 201 USPQ 57, 63, “The known structural relationship between adjacent homologues, for example, supplies a chemical theory upon which a prima facie case of obviousness of a compound may rest.” The homologue is expected to be preparable by the same method and to have generally the same properties. This expectation is then deemed the motivation for preparing homologues. Of course, these presumptions are rebuttable by the showing of unexpected effects, but initially, the homologues are obvious even in the absence of a specific teaching to add or remove methyl groups. See In re Wood, 199 USPQ 137. For example, it is obvious to prepare a methyl substituted compound when the art teaches a hydrogen substituted compound with a reasonable expectation of success. Specifically, methyl and hydrogen are considered homologues and are obvious absent unexpected results. Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to prepare homologs based on the teachings of the preferred embodiments in the prior art. For example, a skilled artisan would be motivated to prepare a methyl substituted
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wherein the pyridine ring is substituted with a methyl group instead of a hydrogen as seen in the prior art reference of Villemure, et al. (WO 2023/018648 A1). A strong prima facie obviousness has been established.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 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 42-43 are rejected under 35 U.S.C. 112(a) or 112, first paragraph, while being enabling for a method of degrading protein which is expressed from the SMARCA2 gene or a method of degrading protein which is expressed from the SMARCA4 gene does not reasonably provide enablement for a method of modulating protein which is expressed by either the SMARCA2 gene or the SMARCA4 gene. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. § 112, first paragraph, have been described. They are:
1. the nature of the invention,
2. the state of the prior art,
3. the predictability or lack thereof in the art,
4. the amount of direction or guidance present,
5. the presence or absence of working examples,
6. the breadth of the claims,
7. the quantity of experimentation needed, and
8. the level of the skill in the art.
The nature of the invention
The nature of the invention is a method of degrading protein which is expressed from the SMARCA2 gene or a method of degrading protein which is expressed from the SMARCA4 gene. Support for the intended use is found in in vitro data for SMARCA2 and SMARCA4 Degradation Assay on pages 304-318 of the specification.
The state of the prior art and the predictability or lack thereof in the art
The state of the prior art is that the pharmacological art involves screening in vitro and in vivo to determine which compounds exhibit the desired pharmacological activities (i.e. what compounds can treat which specific disease by what mechanism). There is no absolute predictability even in view of the seemingly high level of skill in the art. The existence of these obstacles establishes that the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any therapeutic regimen on its face.
The instant claimed invention is highly unpredictable as discussed below:
It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F. 2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is the more specific enablement is necessary in order to satisfy the statute. In the instant case, the instant claimed invention is highly unpredictable since one skilled in the art would recognize that in regards to therapeutic or prophylactic effects of any condition modulating (activating and/or inhibiting) protein expressed from SMARCA2 and/or SMARCA4 , whether or not the condition is affected by the instant compounds' activity would make a difference.
For example, Applicants claims are drawn to modulating protein which is expressed from the SMARCA2 gene and/or SMARCA4 gene. It is well known in the art that the SMARCA family proteins are classified into 8 different types. There are the SMARCA1, SMARCA2, SMARCA3, SMARCA4, SMARCA5, SMARCA6, SMARCAD1 and SMARCAL1. The SMARCA2 has the function involved in transcriptional activation and repression of select genes by chromatin remodeling and SMARCA4 has the function of altering chromatin structure; mutually exclusive factor of the core subunit of the SWI/SNF complex with SMARCA2. SMARCA 2 gene has been associated with various cancers. It is not advisable to inhibit SMARCA2 because it could lead to increased levels of aberrant SMARCA4 components while depleting normal SMARCA2 components, potentially exacerbating cancer progression (see Guo, et al. European Journal of Medicinal Chemistry 286 (2025) 117219).
There is no absolute predictability even in view of the seemingly high level of skill in the art. The existence of these obstacles establishes that the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any therapeutic regimen on its face.
The amount of direction or guidance present and the presence or absence of working examples
The only direction or guidance present in the instant specification is minimal. There are no working examples present for modulating SMARCA2 or SMARCA4. Applicant have only provided working examples for degrading these proteins not modulating.
Test assays and procedure are provided in the specification such as in vitro data for SMARCA2 and SMARCA4 Degradation Assay on pages 304-318.
Receptor activity is generally unpredictable and the data provided is insufficient for one of the ordinary skill in the art in order to extrapolate to the other compounds of the claims. It is inconceivable as to how the claimed compounds can treat the extremely difficult diseases embraced by the instant claims.
Applicants have not provided any competent evidence or disclosed tests that are highly predictive for the pharmaceutical use of the instant compounds. Pharmacological activity in general is a very unpredictable area. Note that in cases involving physiological activity such as the instant case, “the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved.” See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
The breadth of the claims
The breadth of the claims is a method of modulating or degrading protein which is expressed from the SMARCA2 gene or a method of modulating or degrading protein which is expressed from the SMARCA4 gene.
The quantity of experimentation needed and the level of the skill in the art
The quantity of experimentation needed is undue experimentation. One of skill in the art would need to determine what diseases would be benefited by the effects of inhibiting or activating SMARCA2 or SMARCA4 and would furthermore then have to determine which of the claimed compounds in the instant invention would provide treatment or prevention of the diseases.
The level of skill in the art is high. However, due to the unpredictability in the pharmaceutical art, it is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro or in vivo screening to determine which compounds exhibit the desired pharmacological activity and which diseases would benefit from this activity.
Genentech Inc. v. Novo Nordisk A/S (CA FC) 42 USPQ2d 1001, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in undue experimentation to test which diseases can be treated by the compound encompassed in the instant claims, with no assurance of success.
This rejection can be overcome, for example, by amending the claim to read on the subject matter that Applicants' specification are enabled for as indicated above. Applicants should delete the terms “modulating or” in claims 42 and 43.
IV. Objections
Dependent Claim Objections
Dependent Claim 35 is objected to as being dependent upon a rejected based claim. To overcome this objection, Applicant should rewrite said claims in an independent form and include the limitations of the base claim and any intervening claim.
V. Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Shawquia Jackson whose telephone number is 571-272-9043. The examiner can normally be reached on 7:00 AM-3:30PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Adam Milligan can be reached on 571-270-7674. 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://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
/SHAWQUIA JACKSON/Primary Examiner, Art Unit 1626
