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 .
Priority
This application claims the benefit of and priority of PCT/CN2022/135909 filed 12/01/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on the following dates: 3/20/2024, 7/31/2024, 11/28/2024, 3/4/2025, and 8/3/2025 was filed prior to the mailing of the instant first Office Action on the merits. The submission is in compliance with the provisions of 37 CFR 1.97 and is acknowledged.
Claim Objections
Claim 16 is objected to because of the following informalities: The examiner objects to the naming convention of the compounds contained within the instant claim 15. Several compounds are identified with an alphanumeric identifier and other compounds . Appropriate correction is required.
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.
Claim 19 and 20 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 preventing and/or treating "…breast cancer, lung cancer, ovarian cancer, rectal cancer, …and malignant pleural mesothelioma" where mutations in the NF2 and LATS1/2 can cause these proteins to no longer function (instant ¶5 and Bordas p1, lines 20-35); in a subject in need thereof, comprising the administration of compound formula (1) or acceptable salt of claim 1, does not reasonably provide enablement for the treatment of ALL cancers that currently exist. 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. The instant clams are drawn to a method of preventing and/or treating cancer in a subject in need thereof, where the method comprising administering the compound of formula (I), the pharmaceutically acceptable salt thereof, or the solvate of the pharmaceutically acceptable salt according to Claim 1. The instant specification fails to provide information that would allow the skilled artisan to practice the treatment of all cancers that exist.
[In re Sichert, 196 USPQ 209 (CCPA 1977)]
To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re
Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). Explaining what is meant by “undue
experimentation,” the Federal Circuit has stated:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).'
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404
where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547
the court recited eight factors:
the quantity of experimentation necessary, the amount of direction or guidance provided,
the presence or absence of working examples,
the nature of the invention,
the state of the prior art,
the relative skill of those in the art,
the predictability of the art, and
the breadth of the claims.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA
1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands
factors are relevant to the instant fact situation for the following reasons:
The nature of the invention, state and predictability of the art, and relative skill level
The invention relates to a method of preventing and/or treating cancer in a subject in need thereof, where the method comprising administering the compound of formula (I), the pharmaceutically acceptable salt thereof, or the solvate of the pharmaceutically acceptable salt according to Claim 1. The relative skill of those in the art is high, that of an MD or PHD. That factor is outweighed, however, by the unpredictable nature of the art. As illustrative of the state of the art, the examiner cites that while applicant demonstrated treatment in the four aforementioned cancer cell lines, applicant failed to treat a variety of other cancers that are encompassed by applicant's claims. Moreover, given that different cancers possess contrasting etiology, the examiner maintains that what is applicable to one cancer is not applicable to every single cancer in existence. Additionally, the examiner contends that various types of cancers have different causative agents, involve different cellular mechanisms, and consequently, differ in treatment protocol. Such arguments are supported by El-Sayes et al. (see El-Sayes et al., ”Tumor Heterogeneity: A Great Barrier in the Age of Cancer Immunotherapy”, Cancers, Vol. 13, No.4, February 21, 2021) who teach about the art and the challenge of cancer treatment which is to target specific therapies to pathogenetically distinct tumor types, to maximize efficacy and minimize toxicity. Cancer classification has been based primarily on morphological appearance of the tumor and that tumors with similar histopathological appearance can follow significantly different clinical courses and show different responses to therapy (El-Sayes et al., ”Tumor Heterogeneity: A Great Barrier in the Age of Cancer Immunotherapy” Cancers, Vol. 13, No.4, February 21, 2021). There is no absolute predictability even in view of the seemingly high level of skill in the art. As a result, the examiner maintains that applicant has not enabled the breadth of the claims.
The breadth of the claims
The claims are thus very broad insofar as they recite the “treatment of every single cancer in existence”. While such “treatment” might theoretically be possible for some cancers such as lung, myeloma and pancreatic cancer, as a practical matter it is nearly impossible to achieve a treatment for all possible cancers utilizing every single compound of formula I. The scope of compounds encompassed by formula I is also extensive.
The amount of direction or guidance provided and the presence or absence of working examples
The specification provides support regarding MSTO-211H and NCI-H2052 lung cancer cells and the inhibitory factors of the disclosed embodiments for the compositions of Formula (I). Specifically, Effect example 1: Tumor cell proliferation inhibition experiment, where the Cell Titer Glo Luminescent cell viability assay kit was used, with results to demonstrate the present disclosure to have good inhibitory activity (¶1183-1186). Additional support can be found in support of the applicant’s findings, in that YAP/TAZ targeted inhibitors to be used in the treatment for cancers which include pleural mesothelioma, lung and breast cancers. Maille et al (A defect of maphiregulin release predicted longer survival independently of YAP expression in patients with pleural mesothelioma in the IFCT-0701 phase 3 trial, Molecular Cancer Biology, vol 150, issue 11, doi.org/10.1002/ijc.3997, 3/9/2022) correlates the use of YAP/TAZ inhibitors to treat cancer lines and to determine efficacy in treatment defined in “2.2 Materials and Methods”(p1891) and “Results” section 3.2 “YAP transcriptional coactivator tumor expression was also associated with better prognosis in MPM patients from the MAPS trial” (p1894).
The quantity of experimentation necessary
Due to the known unpredictability of the art, where tumor heterogeneity has been a barrier to all cancer treatments, no one skilled in the art would accept the assertion that every single compound of Formula (I) could be predictably used in the treatment of all cancers as inferred by the instant claims and detailed in the specifications. The instant claims identify “…preventing and/or treating cancer…” with identification of the following cancers within the specification known to have changes to expression and/or increases to YAP/TAZ-TEAD pathways: breast, lung, ovarian, rectal, pancreatic, prostate, gastric, esophageal, liver cancers and malignant pleural mesothelioma (p1, ¶5). Therefore, Formula (I) could not be used for the treatment of all cancers as inferred by the instant claims and the specification. Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the invention claimed in the patent a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success as to which types of cancers would be responsive to an inhibitor specific to the YAP/TAZ-TEAD pathways.
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.
Claim 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 identify the compounds as identified in claim 16 (instant claims). As identified, multiple compounds have multiple naming conventions making it unclear as to which structure coincides with the applicant’s naming convention. For example, on p.82, the compounds have two distinct names referencing the same compound (row 1, #3) as “55a1 or 55a2”. See also p. 77 top row where a single compound is labeled 41a1 or 41a2. Similarly, examples included on p.78, where four compound names are used to identify the same compound structure (row 2, #1-3) as “45a1, 45a2, 45a3 or 45a4”. Therefore, it is unclear as to intent or identification of the specific compound is meant to be interpreted as two different compounds or if the intent is to claim the isomers of the same compound.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-20 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Bordas et al (WO 2021186324A1)
Regarding the claims 1-18, Bordas et al. anticipates the compound of Formula I as identified by the instant claim. The art discloses the identical compound of Formula I (p3, line30), and further discloses the following:
W= O,
X=CH and N,
Y=CH and N,
Z=CH2, O and NH,
A= 5- or 6-membered aromatic heterocyclic ring,
Q= is selected from; (i) -C(R7)2-N(R8)-R11; (ii) 9- or 1 a-membered partially saturated heteroaryl comprising at least one N heteroatom; (iii) 4-, 5- or 6-membered saturated heterocyclic ring comprising at least one heteroatom or heteroatom group selected from N, 0, S, -S(=O) and -S(=0)2, with the proviso that at least one N heteroatom is present, wherein the heterocyclic ring is unsubstituted or substituted with one or more substituents independently selected from hydroxy, C1-C3alkyl, C1-C3alkoxy, halo and C1-C3alkylene forming a bridge between two ring atoms of the saturated heterocyclic ring, thus forming a bridged bicyclic structure,
(p5, line 10) as identified in the instant claim 1. Bordas et al. further demonstrated as preparations to the Examples 42a and 54b (p261-273) of the reference art, the compounds identified as 59 and 59a (cited from ISR on page 265).
Regarding claims 19-20, Bordas et al. anticipates the methods of preventing and/or treating cancer in a subject by the administration of the compound of formula I (instant claim 19) or the pharmaceutical composition (instant claim 20). Bordas et al, identifies in (Summary of the Invention, p3, line23) where the invention further provides methods treating, prevention or ameliorating cancers comprising administering to a subject in need thereof an effective amount of a YAP/TAZ-TEAD PPI inhibitor. This is further supported as “Diseases and Disorders and Methods of Use”, regarding the targeting of diseases with inhibition YAP/TAZ-TEAD interactions, for the identified cancers specifically pleural mesotheliomas, breast cancer, lung cancer and ovarian cancer (p69, lines 23-38). Bordas et al. identifies in Claim 35 (reference art) as “A method of treating a cancer or tumor in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of a compound of formula (I)...” Bordas et al. further discloses data to support where (p368, line 35 through p372, line 5), “The results indicate that the compounds may therefore be useful in the treatment of diseases or conditions mediated by the YAP overexpression and/or YAP amplification and/or YAP/TAZ-TEAD interaction, such as cancers.”
Summary of the Claims
Claims 1-20 are pending.
Claims 1-20 are rejected.
No claims are in condition for an allowance.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEVE DROUIN whose telephone number is (571)272-5426. The examiner can normally be reached Monday- Friday 7:30am-5:00pm.
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/S.H.D./Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627
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