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
Instant application 18/275/850 filed on 08/04/2023 claims benefit as follow:
CONTINUING DATA:
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Status of the Application
Claims 1-3, 7, 10-15, 17, 20-21 are pending.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/04/2023 was in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 20 and 21 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 treating specific cancers, does not reasonably provide enablement for preventing any disease, disorder or condition. 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.
This is a scope of enablement rejection.
Although enabled for treatment of specific cancer (instant specification Table 1 and Examples 1-8), the claims are not enabled for prevention of any cancer.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill;(E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure (MPEP 2164).
The instant claims are very broad, directed to both preventing and treating “a disease, disorder or condition”. It should be noted that claim 20 is directed to a method of preventing and treating any disease, disorder or condition and claim 21 limits the disease, disorder or condition to “cancer”.
A disclosure should contain representative examples which provide reasonable assurance to one skilled in the art that ensure that the inventor had possession, as of the filling date of the application, of the specific subject matter claimed by him.
The instant invention (see page 1, lines 15-25) is directed to
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As evidenced by Ashraf (J. Ashraf et al., Journal of Molecular Structure 1218 (2020) 128458) “Flavonoids occupy a special place in the realm of natural and synthetic organic chemistry owing to their useful biological activities such as antioxidant [20,21], anxiolytic [22], anticancer, analgesic and antiinflammatory, antimicrobial [23] and enzyme inhibition assays [24]. Since prehistoric times flavonoids have been used for the treatment of diabetes mellitus. Few papers report the inhibition of flavonoids against ɑ-amylase and ɑ-glucosidase [25e27]. In a broader sense, the number of reported flavonoids holds strong antioxidant activity [28e30] by scavenging hydroxyl radicals, lipid per oxyradicals and superoxide anions [31].” (see page 2, left column, last paragraph).
Regarding treatments of cancers, even in the area of cancer treatment, the prior art teaches that “targeting a single hallmark or pathway with a single drug (‘magic bullet’) will not likely lead to cancer cure.” See Zugazagoitia et al., Clin. Ther. 2016;38(7):1551-66 at page 1564. This reference discloses (see, e.g., Table I at page 1554 and Table II at page 1556, as well as the discussion thereof) that different cancers are treated with different drugs, so one would not find it credible that the drugs of the instant claims would be useful in treating all cancers.
With respect to the definition of “prevention”, the claims are given their broadest reasonable interpretation.
The Oxford English Dictionary defines the verb “to prevent” as “to preclude the occurrence of (an anticipated event, state, etc.); to render (an intended, possible, or likely action or event) impractical or impossible by anticipatory action; to put a stop to” (definition II.9.a). “Preventing” as recited in the instant claims, is interpreted to mean the complete and total blocking of all symptoms of a disease for an indefinite period of time. Merely making the disease less likely would not render the disease impossible and thus not qualify as preventing.
In order to prevent a disease: one would need to precisely identify those subjects likely to acquire such a disease, administer Applicant’s claimed invention, and demonstrate that the patient did not develop the cancer as a result of the administration of the claim invention. The specification does not provide any guidance for selecting a population.
Despite some notable successes, there are still relatively few agents approved for cancer prevention (abstract, Andrew R. Reynolds et. al., Cancer Discov (2023) 13 (5): 1058–1083).
Reynolds teaches that “the premise of chemoprevention is sometimes based on the concept that many cancers are preceded by an identifiable phase of “premalignant disease” and that, during this phase, a medicine might be used to prevent the transition to malignant disease; it can also be based on the concept that cancer develops in individuals with specific risk factors where, again, it may be appropriate to intervene with a medicine to prevent cancer. There are many different examples of premalignant disease and many different examples of specific risk factors. An example of the former is preinvasive precursor lesions, such as colonic polyps, which are precursor lesions to colorectal cancer (14, 15). An example of the latter is people with genetic predisposition to cancer, such as women with a
germline BRCA1 mutation (gBRCA1m) or BRCA2 mutation (gBRCA2m) who are at increased risk of breast and ovarian cancers, also known as hereditary breast and ovarian cancer (HBOC) syndrome.” (See page 1058, right column, second paragraph, Andrew R. Reynolds et. al., Cancer Discov (2023) 13 (5): 1058–1083).
Reynolds further teaches that there are considerable challenges to address and barriers to overcome when developing medicines for cancer prevention including patient identification, risk stratification, and safety/tolerability profile for cancer prevention and longer-term safety monitoring (Figure 4).
Moreover, Reynolds teaches that the safety and tolerability of medicines for cancer prevention
is a significant challenge: “Most individuals eligible for cancer prevention will be healthy and asymptomatic, and the use of medicines with serious side effects will be difficult to justify in terms of the risk–benefit ratio” (page 1071, under Patient Safety).
The specification has provided no working examples of preventing any cancer. The only information in the specification are data related to cancer cell lines (Table 1 and Examples 1-8). Moreover, the specification does not provide examples of methods for treatment or prevention of other diseases, disorders or conditions.
Further, the specification does not provide any guidance for selecting a population or any data about risk-benefit ratio for treatments of healthy subjects.
Furthermore, the specification does not provide directions about the length of the preventive treatment. Prevention of a disease is not the same as treatment. In order to prevent a disease, as opposed to merely delaying or reducing symptoms, a method must either render the subject completely resistant to said disease after a limited number of treatments, or, when continued indefinitely, continue to suppress the occurrence of that disease.
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. The specification does not enable any skilled in the art to which it pertains, or with it is most nearly connected, to use the invention commensurate in scope with the claim. Considering the lack of guidance in the specification, one of ordinary skill in the art would be burden with undue experimentation to practice the invention commensurate in the scope of the instant claims.
The examiner suggests limiting the instant claims to methods of treating the specific cancers listed in Table 1 of the instant specification.
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 1-3, 7, 10-15, 17, 20-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4,8,11-21,23 and 26-27 of copending Application No. 18/275,847 (reference application) in view of Wang Wang (Jubo Wang, Tinghan Li, Tengteng Zhao, Tizhi Wu, Chuang Liu, Hong Ding, Zhiyu Li, Jinlei Bian, Design of wogonin-inspired selective cyclin-dependent kinase 9 (CDK9) inhibitors with potent in vitro and in vivo antitumor activity, European Journal of Medicinal Chemistry,Volume 178, 2019, Pages 782-801),
The claims of 18/275,847 recite flavone analogues of Formula (I) and a method of treating or preventing cancer.
Application No. 18/275,847
Instant Compounds
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The claims of 18/275,847 recite:
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The compounds recited in claims of the reference application and the instant compounds of Formula (I) differ only in the position corresponding to instant Z variable.
The compounds of 18/275,847 bear Z connected to a phenyl through a linker (-(CH2)n , wherein n=1-6) , whereas in the instant compounds Z is directly connected to a phenyl group.
However, Wang (Jubo Wang, Tinghan Li, Tengteng Zhao, Tizhi Wu, Chuang Liu, Hong Ding, Zhiyu Li, Jinlei Bian, Design of wogonin-inspired selective cyclin-dependent kinase 9 (CDK9) inhibitors with potent in vitro and in vivo antitumor activity, European Journal of Medicinal Chemistry, Volume 178, 2019, Pages 782-801) teaches compounds bearing amino group directly connected to a phenyl moiety.
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Applying KSR prong (B) - Simple substitution of one known element for another to obtain predictable results - it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the –(CH2)nZ moiety present in compounds of the copending application for Z connected directly to a phenyl ring as in compounds disclosed by Wang. Since Wang teaches the compounds bearing
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directly connected to a phenyl have antitumor activities (see abstract), a person of ordinary skill in the art would be motivated to prepare additional compounds useful for treatments of cancers and would expect retention of activity.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Citation of Background Prior Art
Wang (Jubo Wang, Tinghan Li, Tengteng Zhao, Tizhi Wu, Chuang Liu, Hong Ding, Zhiyu Li, Jinlei Bian, Design of wogonin-inspired selective cyclin-dependent kinase 9 (CDK9) inhibitors with potent in vitro and in vivo antitumor activity, European Journal of Medicinal Chemistry,Volume 178, 2019, Pages 782-801) teaches compounds bearing oxygen derived substituents at the positions corresponding to instant R1, R2 and R4 have antitumor activities (see abstract and Scheme 2):
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Further, Ashraf (Jamshaid Ashraf, Ehsan Ullah Mughal, Amina Sadiq, Nafeesa Naeem, Syed Aun Muhammad, Tahira Qousain, Muhammad Naveed Zafar, Bilal Ahmad Khan, Muhammad Anees, Design and synthesis of new flavonols as dual ɑ-amylase and ɑ-glucosidase inhibitors: Structure-activity relationship, drug-likeness, in vitro and in silico studies, Journal of Molecular Structure, Volume 1218, 2020, 128458) teaches flavones bearing halo (Br) in a position corresponding to the instant R4 variable and OH in position corresponding to the instant R5 variable.
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In addition, WO 2015/112898-A1 teaches compounds of Formula I useful for treating cancer (see pages 14/15):
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wherein, among others, X is O; Y is CR1; D1 is OH or OR, R1 (corresponding to instant R1 and R5 variables) is hydroxyl, D (corresponding to instant R2 and R4) is selected from H, OH, OR and halogen, and
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Starting from Wang a person of ordinary skill would have to simultaneously substitute the OH (instant R4 position) and H (instant R5 position) in Wang’s compound 24b to arrive at the compounds of the instant formula (I).
Compounds bearing halo (Br) in position corresponding to instant R4 and -OH in position corresponding to instant R5 variables have been disclosed by Ashraf. However, starting from Wang a person of ordinary skill would have to perform the two modifications simultaneously.
It should also be noted that the instant claims are limited to specific R4 and R5 substituents.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IZABELA SCHMIDT whose telephone number is (703)756-4787. The examiner can normally be reached Monday - Friday from 9 am to 5 pm.
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/I.S./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621