ETAILED ACTION
Non-Final Rejection
Notice of Pre-AIA or AIA Status
1. 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
2. Applicant's election with traverse of Group I claims 1-6 in the reply filed on 04/09/2026 is acknowledged. The traversal is on the ground(s) that the method claims of Group II (claims
7-15) are drawn to administering the pharmaceutical combination product of claim 1.
Thus, there is no undue burden on the Examiner to search the complete claim set.
This is not found persuasive because the technical feature “pharmaceutical combination product of claim 1 comprising a parvovirus (a protoparvovirus) and Benzimidazole derivate” is rendered obvious by the combined prior art teachings (see, restriction office action 12/10/2025) and thus lack unity of invention under PCT rule 13.1 with Group II claims 7-15 reciting method of administering the claimed pharmaceutical composition.
Election of species:
the protoparvovirus H-1PV, and
Benzimidazole derivative Ledipasvir (Formula Ia).
The requirement is still deemed proper and is therefore made FINAL.
Status of Claims
3. Claims 1-15 are pending.
4. Claims 7-15 are withdrawn from examination due to Restriction/Election.
5. Claims 1-6 are under examination.
Priority
6. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. EP20216171.7, filed on 11/21/2020.
This application is 371 of PCT/EP2021/086283 filed on 12/16/2021.
Information Disclosure Statement
7. The information disclosure statement (IDS) submitted on 11/09/2023 on is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
8. 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.
The instant specification listed 28 references on page numbers 27-29.
Claim Interpretation
9. The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim 1: A pharmaceutical combination product comprising: (a) a protoparvovirus, wherein said protoparvovirus is H-1 (H-1PV) or a related rodent protoparvovirus selected from LuIII, Mouse minute virus (MMV), Mouse protoparvovirus (MPV), Rat minute virus (RMV), Rat protoparvovirus (RPV) or Rat virus (RV); and (b) an antiviral benzimidazole derivative of Formula I. The elected species of benzimidazole derivative is Formula I (known as Ledipasvir and licensed by US FDA). Based on the instrant specification, it is interpreted that H-1PV and benzimidazole derivative is Formula I (Ledipasvir) may be used in combination or individually as a pharmaceutical composition for treatment of cancer or other disease conditions.
Claim Rejections - 35 USC § 103
10. 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 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.
11. Claims 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Marchini et al 2019 (US20190076494A1, 03/14/2019) and further in view of Camden et al 2020 (AU763272B2, 07/07/2003), Son et al 2020 (Immune Netw. 2020 Aug 4;20(4): e29), Li et al 2017 (Antiviral Research 142 (2017) 83e12), Ioannou et al 2018 (Journal of Hepatology, Volume 68, Issue 1, January 2018, Pages 25-32), Idilman et al 2019 (Journal of viral hepatitis, 26(6), 666-674), Scott et al 2018 (A Review in Chronic Hepatitis C. Drugs (2018) 78:245–256), and US FDA 2014 (Attached PDF printout U.S. Food and Drug Administration Approves Gilead’s Harvoni® (Ledipasvir/Sofosbuvir).
Claims 1-6: Marchini et al 2019 is in the art and disclosed a pharmaceutical composition comprising a parvovirus (or parvotherapeutic agent) in an effective dose and combined with an acceptable carrier (See, para [0100]); parvoviruses, H-1PV or a related rodent parvovirus selected from the group consisting of LuIII, Mouse minute virus (MMV), Mouse parvovirus (MPV), Rat minute virus (RMV), Rat parvovirus or Rat virus (RV) for the treatment of lung cancer (See, abstract, claims 1-3).
Marchini et al 2019 suggested the parvovirus is in combination with a chemotherapeutic agent (see, para [0103]). Chemotherapeutic agents useful in combination with the parvovirus for the purposes of the present invention include all chemical compounds that are effective in inhibiting tumor growth, and the parvovirus and the chemotherapeutic agent are administered as separate compounds. (see, para [0111], claim 3).
Marchini et al 2019 does not teach Benzimidazole derivative Ledipasvir (Formula Ia).
Camden et al 2020 teaches Benzimidazole derivatives for the treatment of viral infections and cancer. The composition contains a benzimidazole derivative, the pharmaceutically acceptable salts thereof or mixtures thereof with other viral and cancer treatments. The "anti-cancer compounds" are benzimidazole derivatives, and their salts. (See, abstract, Description, Claims 1-18).
Son et al 2019 teaches the antitumor potentials of Benzimidazole anthelmintics as repurposing drugs (See, abstract, figure 1, entire article).
Both Camden et al 2020 and Son et al 2019 do not explicitly disclose the instant claimed (instant claims 1-6) Benzimidazole derivative Ledipasvir (Formula Ia).
The chemical structure of Ledipasvir (as recited below) is known in the prior art before the effective filing date of the claimed invention because US FDA has approved Ledipasvir in 2014 for treatment of chronic HCV infection (See, US FDA 2014 and attached pdf printout).
Li et al 2017 is in the art and reviewed current therapy for chronic hepatitis C disease (caused by HCV) and the role of direct-acting antivirals and beneficial effect on HCV hepatocellular carcinoma in HCV chronically infected patients (see, page 101 table 11, page 102, table 12, entire article) and disclosed chemical structure of Ledipasvir as recited below (See, Li et al 2017, page 90 structure number 22 Ledipasvir).
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Ioannou et al 2018 disclosed Hepatitis C virus (HCV) eradication induced by direct-acting antiviral (e.g. Ledipasvir) reduces the risk of hepatocellular carcinoma (See, abstract, entire article).
Idilman et al 2019 teaches low recurrence rate of hepatocellular carcinoma following ledipasvir and sofosbuvir treatment in a real-world chronic hepatitis C patient’s cohort (See, abstract).
Scott et al 2018 has reviewed Chronic Hepatitis C virus infection treatment with Ledipasvir/Sofosbuvir and Hepatocellular Carcinoma and concluded that ledipasvir/sofosbuvir (± ribavirin) is a valuable effective and generally well tolerated option for adolescent and adult patients with HCV (See, abstract).
Based on the combined prior art teachings as recited supra the above (i) proto-parvoviruses including elected species H-1PV are oncolytic, (ii) Benzimidazole derivative including elected species Ledipasvir (Formula Ia) has cancer inhibition properties. Therefore, based on need and requirement a therapeutics design choice would have been available and would have been obvious to one of the ordinary skills to (i) use the H-1PV and Benzimidazole derivative Ledipasvir (Formula Ia) as a combination to develop a pharmaceutical composition or (ii) to develop an individual pharmaceutical composition of H-1PV and (iii) an individual pharmaceutical composition of Benzimidazole derivative Ledipasvir (Formula Ia) for separate administration for the same patient with a cancer in need of.
See, MPEP 2144.06: COMBINING EQUIVALENTS KNOWN FOR THE SAME PURPOSE.
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious); and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine).
It would have been obvious to one of the ordinary skills in the art to modify the prior art teachings of Marchini et al 2019 with additional teachings of Camden et al 2020, Son et al 2020, Li et al 2017, Ioannou et al 2018, Idilman et al 2019, Scott et al 2018 and US FDA 2014 to arrive at the invention of claims 1-6. One of the ordinary skills would have been motivated to develop a combination protoparvovirus H-1PV (oncolytic virus) and Benzimidazole derivative Ledipasvir (US FDA approved drug) based pharmaceutical composition for treatment of cancer, viral origin cancer treatments and for commercial success. There would be a reasonable expectation of success based on the applied prior arts as recited supra and knowledge and skills of the ordinary in the art. This is analogous to some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claims 1-6. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, A, C, G).
Conclusion
12. No claim is allowed.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMADHAN J JADHAO whose telephone number is (703)756-1223. The examiner can normally be reached M-F 8:00-5:00.
14. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas J Visone can be reached at 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAMADHAN JAISING JADHAO/Examiner, Art Unit 1672
/BENNETT M CELSA/Primary Examiner, Art Unit 1600
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