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 .
Priority
This application is a DIV of 17/369,589 dated 07/07/2021. US Pat. 11957667
17/369,589 has PRO 63/049,140 dated 07/08/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 09/28/2023, and 02/16/2024 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of the Application
Claims 1-20 are pending and currently under examination.
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)(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.
(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.
Claims 1-2 and 6-17 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Lee (US Pat. US 8.440,649 B2).
Lee teaches phenanthroindolizidine analogues which exhibit anti-CoV activity, i.e., reducing CoV-induced cytopathic effects or inhibiting viral protein production and viral replication which is used as a method of treating infection by CoV (e.g., SARS-associated virus and transmissible gastroenteritis virus) with a compound of Formula I, wherein the derivative of compound 1 anticipates the structural limitations of instant claims 1-2 and 6-17 wherein the X-Y ring comprises single bonds, Y is N, R1, R4, R5, R8-R15 are H, R2, R3, R6, and R7 are alkoxy (OMe), R16 and R17 are bond, a X is CR’R” wherein R’ and R” are H and n is 1 (Summary, table 1).
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Lee’s compound 1 (Left) Derivative of formula I instant claim 17 (Right)
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Su (Design, synthesis, antiviral activity, and SARs of 13a-substituted phenanthroindolizidine alkaloid derivatives) in view of Wang (Tylophorine Analogs Allosterically Regulates Heat Shock Cognate Protein 70 And Inhibits Hepatitis C Virus Replication) and further in view of Lee (US Pat. US 8.440,649 B2).
The instant claims are directed to a method of treating a disease caused by a positive strand RNA virus comprising identifying a subject suffering from the disease, and administering to the subject an effective amount of a compound of Formula I.
In addition to the disclosures of Lee above, Su et al. teach the phenanthroindolizidine alkaloid compound of (R)-tylophorine, registry number 25908-92-3 which meets the structural limitations of the compound of formula I of the instant claims wherein the X-Y ring comprises single bonds, Y is N, R1, R4, R5, R8-R15 are H, R2, R3, R6, and R7 are alkoxy (OMe), R16 and R17 are bond, a X is CR’R” wherein R’ and R” are H and n is 1 (fig. 1).
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Su discloses Table 1 and 2 wherein the In vivo antiviral activity of tylophorine targeting the positive strand RNA virus of tobacco mosaic virus (TMV) RNA.
However, Su et al. fail to explicitly disclose administering the compound of (R)-tylophorine for the treatment of the positive strand RNA viruses of SARS-CoV-2, Zika, Dengue, HCoV-OC43, or HCoV-229E.
Wang et al. teach tylophorine analogs which exhibit potent inhibitory activity against hepatitis C virus (HCV) replication in genotype 1b Con 1 isolate wherein the HCV replication is partially mediated through cellular heat shock cognate protein 70 (Hsc70) (Abstract). Wang also teaches Hsc70 is associated with the HCV replication complex. Host chaperones and co-chaperones play important functions in the assembly of the viral replication complex and the replication of the viral genome. Hsc70 participated in the RNA-dependent replication of sindbis virus, influenza virus, rotavirus, and dengue virus (Discussion, page 7, 2nd paragraph).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the instant application, to administer a compound of formula I as tylophorine for the treatment of a positive strand RNA virus to a subject in need thereof by combining the anti-TMV teachings of Su with the anti-HCV activity and Hsc-70 participation in the RNA dependent replication of sindbis, rotavirus, and dengue (Flaviviridae family) virus as disclosed by Wang because each of the viruses are positive stranded RNA viruses and Lee teaches compound of tylophorine is useful in treating coronaviruses. See MPEP 2144.06 and MPEP 2143.
A person of ordinary skill in the art would have been motivated to administer an effective amount of the compound of tylophorine to treat a disease caused by a positive strand RNA virus in a subject in need thereof by combining the teachings of treating TMV by Su with the disclosures of treating HCV with tylophorine and how tylophorine affects Hsc-70 in the other positive stranded viruses of sindbis, rotavirus, and dengue (Flaviviridae family) virus by Wang. In light of Lee’s disclosure of a method of treating infection by CoV (e.g., SARS-associated virus and transmissible gastroenteritis virus) with a derivative of Lee’s Formula I (compound 1), a skilled artisan would have had a reasonable expectation of success in treating other positive stranded RNA viruses including the SARS-CoV-2 virus based on the results disclosed by Su and Wang of tylophorine to treat the positive stranded RNA viruses of TMV sindbis, rotavirus, and dengue and further in view of Lee’s disclosure of treating corona viruses. See MPEP 2112and MPEP 2144.05(II).
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, and 6-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. US 7,332,502 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the limitations of claims 1 and 6-17 of the instant application are directed to the same invention as reference claims 1-7. The compound derivatives of formula I of instant claim 17 are satisfied by the reference claims 1-7 wherein compound 2 of the patent anticipate compound 1 of instant claim 17.
Conclusion
All claims are rejected, no claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNESTO VALLE JR whose telephone number is (703)756-5356. The examiner can normally be reached 0730-1700 M-F EST, 1st Friday off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C Milligan can be reached at 571-270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/E.V./Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623