Detailed Action
The present office action is in response to the application filed on 02 Jun 2023.
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 .
Status
Claims 15-32 of the pending application have been examined on the merits. Acknowledgement is made of the cancellation of claims 1-14.
Priority
Applicants identify the instant application, Serial #: 18/039,985, filed 02 Jun 2023, as a National Stage Entry of International Patent Application #: PCT/EP2021/083897, filed 02 Dec 2021, which claims foreign priority from Foreign Application #: EP20306485.2, filed 03 Dec 2020.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 02 Jun 2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 15-32 is/are rejected under 35 U.S.C. § 103 as being unpatentable over US Patent No. 7,425,553, hereinafter ‘553, further in view of Lovering et al. (J Med Chem, 2009, 52:6752-6756), hereinafter Lovering, Vojacek et al. (Chem Med Chem, 2019, 14:853-864), hereinafter Vojacek, Mamedov et al. (Tetrahedron, 2015, 71:9143-9153), hereinafter Mamedov, Andreev et al. (Eur J Med Chem, 2015, 96:250-258), hereinafter Andreev, and Patani et al. (Chem Rev, 1996, 96:3147-3176), hereinafter Patani.
The instant claims are directed to compounds of formula (I) and compositions comprising compounds of Formula (I) and pharmaceutically acceptable excipients (claims 15 and 19):
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The instant claims include limitations of the identity of R1 (claim 16), the position of R1 (claim 17), and named compounds which are species of formula (I) (claim 18). The instant claims also include methods of treating cancer and viral infections by administering a compound of formula (I) or a composition containing formula (I) (claims 20-32).
‘553 teaches Compound 1 (Column 26, lines 50-64; Claim 1):
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‘553 further teaches a pharmaceutical composition of Compound 1 and a pharmaceutically acceptable carrier or vehicle (claim 2). ‘553 further teaches that the compounds of the reference can be administered to treat cancer, including small cell lung cancer, acute myeloid leukemia, Hodgkin’s lymphoma, myelofibrosis, and multiple myeloma (columns 76-77, Table 2). ‘553 also teaches that the compounds of the reference can be administered to treat viral infections including HSV-I, HSV-II, influenza, HIV-I, hepatitis A, and EBV (column 78, lines 45-65). ‘553 further teaches that Compound 1 is cytotoxic to cancer cells in vivo (column 85, lines 5-44). However, ‘553 does not teach the indole moiety of Compound 1 can be tetrahydroindole as in the instant claims.
Lovering teaches that compounds with higher complexity as measured by saturation have the capacity to access greater chemical space (pg. 6755, column 1) and that compounds with greater saturation generally have a higher solubility (pg. 6754, column 2; pg. 6755, column 1).
Vojacek teaches that indoles are commonly used in medicinal chemistry but the planarity of the indole ring is not necessarily optimal for all target enzymes (Abstract). However, the replacement of flat scaffolds by nonplanar molecular cores domination sp3 hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity (Abstract). Vajacek teaches that tetrahydroindoles are suitable for covering less explored space of indoles (Abstract).
Mamedov teaches that the 4,5,6,7-tetrahydro-1H-indole moiety (as found in the instant claims) is known to display a wide spectrum of biological activity including antitumor activity.
Andreev teaches that the 4,5,6,7-tetrahydro-1H-indole scaffold is useful for treating viral infections, specifically HCV.
Patani teaches that bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents and the concept of bioisosterism is often considered to be qualitative and intuitive (pg. 3147, columns 1-2). Patani also teaches that there are opportunities to employ bioisosteres to gain specific insight into the quantitative structure-activity relationships associated with a specific class of drugs (pg. 3148, column 1). Patani further teaches that methyl acts as a replacement for hydrogen according to Grimm’s Hydride Displacement law (pg. 3152, column 1).
MPEP 2144.08(II)(A)(4)(c) states, “closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein).”
Based on the teachings of teachings of ‘553, Lovering, and Vojacek, a person of ordinary skill in the art would modify Compound 1, taught in ‘553, to incorporate a 4,5,6,7-tetrahydro-1H-indole scaffold in place of the indole moiety of Compound 1 and so arrive at compounds of the instant claims. The artisan would be motivated to make this change to create a compound with higher solubility and to avoid the disadvantages of the indole ring such as poor solubility and high promiscuity, as taught by Lovering and Vojacek.
The artisan would further modify Compound 1 by replacing a hydrogen on the indole with a methyl group, as taught by ‘553 and Patani. The artisan would be motivated to make this replacement to gain specific insight into the quantitative structure-activity relationships associated with a specific class of drugs, as taught by Patani.
The artisan would have an expectation of success that the modified Compound 1 would retain the anticancer and antiviral properties because of the similarities between Compound 1 and the compounds of the instant claims. Further, the 4,5,6,7-tetrahydro-1H-indole moiety is known to possess both anticancer and antiviral properties, as taught by Mamedov and Andreev.
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan D. Mahlum whose telephone number is (703)756-4691. The examiner can normally be reached 8:30 AM - 5:00 PM ET, M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached at (571) 272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.D.M./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625