DETAILED 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 Group II, corresponding to claims 29-37, in the reply filed on August 3, 2026, is acknowledged.
Applicant elected the following species: “T620”.
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. Also see STN record below.
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The examiner applied art that he identified during his search in an effort to expedite prosecution on the merits. The species election remains intact.
Information Disclosure Statement
The information disclosure statement filed January 14, 2025, fails to comply with the provisions of 37 CFR 1.98(a)(4) because it lacks the appropriate size fee assertion. It has been placed in the application file, but the information referred to therein has not been considered as to the merits.
Status of the Claims
Claims 1-4, 6, 9, 13, 16, 19-23, and 27-37 are pending. Claims 1-4, 6, 9, 13, 16, and 19-23 are withdrawn for being directed to a non-elected group. Claims 27-37 are examined.
Suggestions for Allowance:
Delete the term “prodrug” from the claims;
Limit the claims to the elected species;
Limit the claims to a form that is for administration to a subject, including a tablet, capsule, pill, gel cap, or other dosage form that is only used for administration to a subject (Spec p33); and
Limit the form to a specific unit dosage such as 5 mg, e.g. (Spec. p36).
Claim Rejections - 35 USC § 112 (Prodrug)
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 27-37 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while provides sufficient written support for salts, solvates, enantiomers, diastereoisomers, and tautomers, does not reasonably provide contemplation for prodrugs of the same. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to makes and use the invention commensurate in scope with these claims. The term prodrug is not enabled in the context of the instant claims when read in light of the instant Specification.
Claims 27-37 is rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement.
The claims contain 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(s), at the time the application was filed, had possession of the claimed invention. Specifically, claim 27 recites a prodrug of a compound of a claimed formula (Va) or (Vb).
The MPEP §2163 states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. In the case of chemical entities, Applicant's attention is further directed to Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568, 43 USPQ2d 1398 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089, 118 S. Ct. 1548 (1998), which holds that an adequate written description requires a precise definition, such as by structure, formula, chemical name, or physical properties, "not a mere wish or plan for obtaining the claimed chemical invention." Eli Lilly, 119 F.3d at 1566. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. Although the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus, if the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. While the MPEP does not define what constitutes a sufficient number of representative species, the courts have indicated what does not constitute a representative number of species to adequately describe a broad generic. For example, in In re Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618.
The Federal Circuit has adopted the standard set forth in the Patent and Trademark Office (PTO) Guidelines for Examination of Patent Applications under the 35 U.S.C. 112.I "Written Description" Requirement ("Guidelines"), 66 Fed. Reg. 1099 (Jan. 5, 2001), which state that the written description requirement can be met by "showing that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics," including, inter alia, "level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention" Enzo Biochem, Inc. v. Gen-Probe Inc., 296 F.3d 316, 1324-25 (Fed. Cir. 2002) (quoting Guidelines, 66 Fed. Reg. at 1106). Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient. MPEP §2163. However, if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP §2163.
The instant claims are drawn to a claimed structure and prodrugs thereof.
Level of skill and knowledge in the art: The level of skill in the art is high.
Partial structure: The claimed structure has been disclosed and example compound species that would be within the claimed structure have been disclosed. However, as to the claimed prodrugs, no specific examples are given that would demonstrate possession of or put the public in possession of the claimed prodrugs of the claimed structure.
Physical and/or chemical properties/Functional characteristics: The compound claimed, including the prodrugs, are compounds which are allegedly useful to antagonize/inhibit ATK kinase. Although the art recognizes the above definitions the terms are not explicitly defined by the specification in such a way as to demonstrate that the inventor had possession of the claimed prodrugs.
Predictability of the Art: It is generally accepted in the art that formation of a particular prodrug for a given compound or series of compounds is unpredictable.
As stated by Stella et al. (Prodrugs: Challenges and Rewards, Part 1, 2007) (attached), the personnel and skills needed for a successful prodrug program “are no different from those for analog development – it takes a team. The ideal drug is one that is active, easy to formulate, well absorbed after oral dosing, has an acceptable PK profile, and is both renally cleared and metabolized to 1-2 non-toxic metabolites that are rapidly excreted after being formed. If a prodrug intervention is necessary, obviously this ideal scenario is not met. The ideal prodrug, therefore, is one that readily achieves its desired goal, is non-toxic, and breaks down efficiently and quantitatively to the drug and known and safe by-products. Like the drug discovery process, this goal is not often met” (Page 24, Paragraph 3, emphasis added).
Method of making the claimed invention: Although the Specification provides a method for making the elected compounds, no method for making a prodrug has been disclosed.
Summary: In the instant case, Applicant has not disclosed the structure, formula, chemical name, or physical properties of the numerous prodrugs of compounds of formula (Va) or (Vb). Although some functional characteristics are disclosed or would be known to a person of ordinary skill in the art, in the absence of a disclosed structure, there can be no correlation between the function and structure of the claimed prodrug compounds.
However, the MPEP states that written description for a genus (for example, the claimed prodrugs or active metabolites of the elected compound species) can be achieved by a representative number of species within a broad generic. It is unquestionable that the claim(s) are broad and generic with respect to all possible compounds encompassed by the claims: the possible structural variations are limitless to any prodrugs of formula (I). In the instant case, however, the Specification does not disclose a sufficient variety of species to reflect this variance in the genus. While having written description of the elected compound and compounds identified in the Specification tables and/or examples, the Specification does not provide sufficient descriptive support for the myriad of compounds embraced by the claims such as, for example, prodrugs.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Claim Rejections - 35 USC § 102
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 27-31 and 34-37 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Abrunhosa et al., “Antifungal activity of a novel chromene dimer,” J Ind Microbiol Biotechnol (2007) 34:787–792, as evidenced by Marren, “Dimethyl sulfoxide: an effective penetration enhancer for topical administration of NSAIDs,” Phys Sportsmed. 2011 Sep;39(3):75-82.
The following compound is taught by STN and is taught by Abrunhosa.
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Abrunhosa teaches compounds that have antifungal activity on Aspergillus spp. Among those compounds with activity includes the following compound shown in Scheme 1 and Table 1.
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The assays prepared compounds in DMSO. As evidenced by Marren, DMSO is considered a pharmaceutical carrier.
As such, claims 27-31 and 34-37 are anticipated by the prior art.
Claims 27-37 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yadav et al., “Amberlyst A-21 : An efficient, cost-effective and recyclable catalyst for the synthesis of substituted 4H-chromenes,” Catalysis Communications 8 (2007) 2208–2211.
Yadav teaches the following product formed.
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Product 3 m above wherein R’ is NO2 and R is hydrogen is the elected species. Yadava concludes, “The notable features of this method are mild reaction conditions, greater selectivity, simplicity in operation, cleaner reaction profiles, low cost and reusability of the catalyst, which makes it an attractive and very useful process for the synthesis of chromenes of biological importance.” Further, the process described included filtering and washing with ethanol. Ethanol at that time was used in a mixture of compounds shown above. Ethanol is also considered a pharmaceutically acceptable carrier. See Spec. p9.
As such, claims 27-37 are anticipated by the prior art.
Claims 27, 29-32, and 34-37 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bouattour et al., “Microwave-assisted practical synthesis of 4-imino-3-phenyl-3,4-dihydro-1H chromeno[2,3-d]pyrimidine-2(5H)-thione derivatives and exploration of their biological activities,” Arkivoc 2017, part iv, 291-302 published online May 29, 2017.
Bouattour teaches chromene derivatives as they have been shown to have potential medicinal value. See p292. The following compounds 3b-4c are shown and were tested as having activity on protein kinases. See below.
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, as well as compound 4c shown below:
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Figure 2 explains and shows the structure of these compound which “are active against tumor cell lines or protein kinases.” See p295. These compounds were subjected to in vitro cancer assays against a panel of 7 tumor lines. Compounds 3b, 3c, and 3f exhibited antitumor activity against numerous cell lines. See p296, last par.
Claims 27, 29-32, and 34-37 are anticipated by the prior art.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 27-32, and 34-37 are rejected under 35 U.S.C. 103 as being unpatentable over Bouattour et al., “Microwave-assisted practical synthesis of 4-imino-3-phenyl-3,4-dihydro-1H chromeno[2,3-d]pyrimidine-2(5H)-thione derivatives and exploration of their biological activities,” Arkivoc 2017, part iv, 291-302 published online May 29, 2027.
Bouattour teaches chromene derivatives as they have been shown to have potential medicinal value. See p292. The following compounds 3b-4c are shown and were tested as having activity on protein kinases. See below.
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, as well as compound 4c shown below:
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Figure 2 explains and shows the structure of these compound which “are active against tumor cell lines or protein kinases.” See p295. These compounds were subjected to in vitro cancer assays against a panel of 7 tumor lines. Compounds 3b, 3c, and 3f exhibited antitumor activity against numerous cell lines. See p296, last par.
Including these agents with an excipient or pharmaceutically acceptable carrier is obvious and would be immediately envisaged by a person of ordinary skill in the art in light of their known and reported antitumor activity against various cell lines. As such, it would be obvious prior to the filing of the instant application to arrive at the claimed products in view of the cited prior art. One would be motivated to do so because using a carrier to administer an active API is obvious as any tablet, capsule, or other form requires carriers for administration are well-known in the art. As such, there is a reasonable and predictable expectation of success in arriving at the claimed products in view of the cited prior art. These carriers are known in the art and described as explained in the Specification in Remington’s Pharmaceutical Sciences. See Spec. p9.
As such, no claim is allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARED D BARSKY whose telephone number is (571)272-2795. The examiner can normally be reached on 9-5 M-F.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JARED BARSKY/Primary Examiner, Art Unit 1628
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