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 .
DETAILED ACTION
This Office Action is responsive to the Response to Election/Restriction and Amendment filed 09/17/2025, which amended claims 3-4, 15, and 17.
Claims 1-17 are pending.
Note: Claim 13, on page 53 of the claim set, should begin on a new line and not directly following the period of claim 12.
Priority
This application claims the following priority:
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Abstract
The abstract of the disclosure is objected to because the abstract is confusing; it appears that the abstract is a machine translation of the original Chinese abstract. For example, it is not clear why the abstract recites, in sentence 1, “provided is application of a poly ADP ribose polymerase inhibitor. . .in the preparation of antiviral agents,” when the poly ADP ribose polymerase inhibitor is the antiviral agent. For further example, the last sentence of the abstract is a confusing run-on sentence that ends by stating “the present inhibitor can effectively inhibiting the viruses.” Moreover, the abstract only references compounds of formulas III-IV when the claims recite compounds of formulas I-IV and additional species of compound outside the scope of formulas I-IV.
A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Election/Restrictions
Applicant’s election without traverse of:
-a compound of formula (III) as the specific poly ADP ribose polymerase inhibitor, and
-beta-coronavirus as the species of virus,
in the reply filed on 09/17/2025, is acknowledged.
In a telephone call to Alisa Ramakrishnan on 10/01/2025, Applicant further elected mefuparib as a species of formula (III), as required by the 07/18/2025, Restriction Requirement.
In the course of the search, the species election of “a poly ADP ribose polymerase inhibitor” was broadened to all species of formula (III). Species of formula (III) were found to be free of the art. As such, the species election of “a poly ADP ribose polymerase inhibitor” was broadened to talazoparib.
Claims 4-6 and 10-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim.
Claims 1-3, 7-9, and 15-17 are examined on the merits herein.
Claim Objections
Claims 1, 3, and 15 are objected to because of the following informalities:
-In independent claims 1 and 15, following “poly ADP ribose polymerase” insert - -(PARP)- -, since dependent claims 2 and 16, for example, reference “poly ADP ribose polymerase” as “PARP.”
-In claim 3, line 5, the following should be inserted following “of formula IV,” - -wherein talazoparib, fluzoparib, simmiparib, IMP4297, BGB-290, and ABT-888 have the following structures, - -.
-In claim 3, in the definition of formula IV, “fm” is depicted prior to “(R41),” which is improper; “fm” should follow “(R41),” such as “(R41)fm”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8-9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
-In claims 8-9, the phrase “comprising the same,” renders the claim indefinite because it is not clear what “the same” is referencing. It is not clear if “the same” is referencing “the poly ADP ribose polymerase inhibitor or a pharmaceutically acceptable salt thereof” or if “the same” is referencing something else.
This rejection can be overcome by deleting “comprising the same.”
Claim Rejections - 35 USC § 112(a)-Scope of Enablement
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 1-3, 8-9, and 15-17 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 a method of treating a disease caused by a beta-coronavirus by administering mefuparib or talazoparib to a patient, does not reasonably provide enablement for a method of treating a disease caused by a beta-coronavirus by administering any poly ADP ribose polymerase (PARP) inhibitor to a patient. 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.
The criteria for enablement set out in the In re Wands, MPEP 2164.01(a), considers the following factors:
Breadth of the Claims
Independent claims 1 and 15 are directed toward a method of treating a beta coronavirus by administering to a patient any poly ADP ribose polymerase inhibitor, wherein dependent claims 3 and 17 further limit the poly ADP ribose polymerase inhibitor as selected from one or more of talazoparib, fluzoparib, simmiparib, IMP4297, BGB-290, ABT-888, a compound of formula I, a compound of formula II, a compound of formula II, and a compound of formula IV:
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As such, the breadth of the claims is great.
Level of Skill in Art
The level of skill in the art is a clinician or an artisan with a PhD.
State of the Prior Art
The prior art teaches that it is known to treat certain viruses by administering PARP inhibitors.
US 2006/0079510 to Hellstrand (PTO-892) teaches a method of treating viral diseases with a PARP1 inhibitor (title, abstract, pg. 13, claim 1).
US 2003/0153559 to Literati Nagy teaches a method of treating a viral disease by administering a PARP inhibitor (title, abstract).
US 5,633,282 to Collins teaches that use of a poly(ADP-ribose) polymerase inhibitor for the treatment of a subject against infection by a virus (abstract; Col. 13, claim 1).
The prior art teaches the instantly claimed compounds.
WO 00/42040 to Webber (IDS of 07/08/2025) teaches compounds of formula (I) as a cancer therapeutic (abstract).
WO 2004/080976 to Martin (IDS of 07/08/2025) teaches compounds of formula II for the treatment of vascular disease, septic shock, ischemic injury, neurotoxicity, hemorrhagic shock, viral infection or diseases ameliorated by the inhibition of the activity of PARP (title, abstract, pg. 95-claim 12).
WO 2018/228205 teaches compounds of formula III (abstract).
WO 2007/1113596 to Boueres (IDS of 07/08/2025) teaches compounds of formula IV for the treatment of cancer, inflammatory disease, reperfusion injuries, ischemic conditions, stroke, renal failure, cardiovascular diseases, vascular diseases, neurodegenerative diseases, retroviral infection, retinal damage, skin senescence, UV induced skin damage, and cancer treatment (title, abstract).
US 2021/0085619 to Baldwin (effectively filed 09/23/2019, PTO-892) teaches a method of treating SARS-CoV-2 or HIV by administering a composition comprising an antiviral nanoparticulate therapeutic agent comprising a nanoparticulate delivery vehicle, one or more antiviral agents associated with the nanoparticulate delivery vehicle, and a virus targeting agent bound to an outer surface of the nanoparticulate delivery vehicle (pgs. 20-21, claims 1, 12-27). Baldwin teaches the virus targeting agent as targeting SARS-CoV-2, [0022]; Fig. 11A).
Baldwin exemplifies a nanoparticle comprising talazoparib (TLZ) (pg. 15-16; Examples 1-2), wherein TLZ is taught as a PARP inhibitor ([0077]). Baldwin teaches TLZ as the most potent PARP inhibitor ([0082]).
Thus, while the prior art teaches treating certain viruses by administering PARP inhibitors, and while the prior art teaches the instantly claimed compounds, the prior art does not explicitly teach a method of treating a beta coronavirus generally by administering any PARP inhibitor, aside from talazoparib.
Predictability in the Art
Rehman (COVID-19 challenges and its therapeutics, Biomed & Pharmacotherapy, published 2021, PTO-892) teaches that the development of new drugs to manage COVID-19 effectively is a challenging and time consuming process. Rehman teaches that COVID-19 treatment is solely based on clinical management through supportive care (abstract).
Rehman teaches that many pharmaceutical agents are being investigated for SARS CoV-2 antiviral activity. The efficacy of these investigational agents for COVID-19 is uncertain, due to lack of established data supporting the significance of any of these agents (pg. 3, “6.”).
Rehman teaches that remdesivir’s clinical impact against COVID-19 is uncertain. Rehman teaches that while chloroquine/hydroxychloroquine have shown positive results, the dosage for use against COVID-19 is high and may have adverse side effects. Rehman teaches that while azithromycin provides treatment of inflammation and inhibits spike protein synthesis, it has severe side effects.
Song (COVID-19 treatment: close to a cure? A rapid review of pharmacotherapies for the novel coronavirus, International Jn of Antimicrobial Agents, PTO-829) teaches that there are no approved therapies for COVID-19, but that frontline clinicians and researchers have been experimenting with several virus-based and host-based therapeutics. Song teaches that a) remdesivir, lopinavis/ritonavir and umifenovir should be initiated before the peak of viral replication, b) ribavirin may be beneficial as an add-on therapy, but is ineffective as monotherapy, c) corticosteroids use should be limited to specific co-morbidities, d) intravenous immunoglobulin is not recommended, e) xuegijing may benefit patients with complications of bacterial pneumonia or sepsis, though the efficacy is unknown, f) and that chloroquine and hydroxychloroquine have shown inhibition of SARS-CoV-2, but their clinical efficacy is unknown (abstract).
Song concludes by stating that supportive care remains the cornerstone of COVID-19 management. Song teaches that remdesivir might be considered early in the course of illness, and that other referenced treatments are due to case reports and cannot be generalized for a larger population (pg. 6, “4.”).
In view of the state of the prior art, as discussed above, and the teaching of Rehman and Song, the treatment of coronavirus infection is unpredictable.
Working Examples
Example 1, beginning on pg. 81, teaches the detection of in vitro anti-SARS-CoV-2 activity of mefuparib hydrochloride (CVL218). Mefuparib hydrochloride and Olaparib are taught as inhibiting the replication of SARS-CoV-2 (pg. 83), however Olaparib is outside the scope of the instant claims, and specifically outside the scope of instant formula (II).
Example 2, beginning on pg. 85, tests the cytotoxicity of mefuparib hydrochloride and concludes that mefuparib hydrochloride at 30 mM has no inhibitory effect on the cells, and basically no toxicity, and thus has good safety (pg. 87).
Example 3, beginning on pg. 87, demonstrates that mefuparib hydrochloride can partially antagonize viral entry and significantly inhibits the replication after viral entry, and may be an advantageous potential drug for the treatment of COVID-19 (0g. 89)
Example 4, beginning on pg. 89, provides in vitro evidence that mefuparib hydrochloride is a potential therapeutic agent for treating proinflammatory responses induced by SARS-CoV-2 infections.
Example 5, beginning on pg. 91, demonstrates the metabolism and safety profile of mefuparib hydrochloride in rats.
Thus, the instant examples are limited to testing a single virus, SARS-CoV-2 and a single compound, mefuparib hydrochloride. None of the examples provide in vivo results.
Direction and Guidance
In view of the unpredictability in the art, the lack of teaching of PARP inhibitors in treating coronavirus, and the instant examples which are limited to a method of treating, in vitro, SARS-CoV-2 cells with mefuparib hydrochloride, the instant specification lacks sufficient direction and guidance to use the instant method as claimed.
Quantity of Experimentation
The amount of experimentation required to determine which PARP inhibitors effectively treat which beta coronaviruses, in vivo, would be astronomical and result in an undue amount of experimentation. Such experimentation amounts to invention and not development.
Thus, while being enabling for a method of treating a beta-coronavirus by administering mefuparib or talazoparib to a subject, the specification does not reasonably provide enablement for a method of treating a beta-coronavirus by administering any poly ADP ribose polymerase (PARP) inhibitor to a subject.
Claim Rejections - 35 USC § 103
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 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.
Claims 1-3, 8-9, and 15-17 are rejected under 35 U.S.C. 103 as being unpatentable over US 2021/0085619 to Baldwin (effectively filed 09/23/2019, PTO-892) in view of US 2006/0079510 to Hellstrand (published 2006, PTO-892), US 2003/0153559 to Literati Nagy (published 2003, PTO-892), and US 5,633,282 to Collins (published 1997, PTO-892).
Baldwin teaches a method of treating COVID-19 or HIV/AIDS (pg. 20, claim 22) by administering a first and second nanoparticulate delivery vehicle, wherein each vehicle comprises an active agent (pg. 20, claims 16, 17, 21 and 22).
Specifically, Baldwin teaches a method of treating SARS-CoV-2 or HIV by administering a composition comprising an antiviral nanoparticulate therapeutic agent comprising a nanoparticulate delivery vehicle, one or more antiviral agents associated with the nanoparticulate delivery vehicle, and a virus targeting agent bound to an outer surface of the nanoparticulate delivery vehicle (pgs. 20-21, claims 1, 12-27). Baldwin teaches the virus targeting agent as targeting SARS-CoV-2, [0022]; Fig. 11A).
Baldwin exemplifies a nanoparticle comprising talazoparib (TLZ) (pg. 15-16; Examples 1-2), wherein TLZ is taught as a PARP inhibitor ([0077]). Baldwin teaches TLZ as the most potent PARP inhibitor ([0082]).
Regarding claims 1 and 15, while Baldwin teaches a method of treating SARS-CoV-2 by administering to a subject a composition comprising an antiviral nanoparticulate composition and teaches a nanoparticle comprising TLZ, it differs from that of instant, independent claims 1, 10, and 15 in that it does not exemplify a method of treating SARS-CoV-2 by administering to a subject, a nanoparticulate comprising TLZ.
Hellstrand teaches a method of treating viral diseases by administering a PARP1 inhibitor to a subject (title, abstract, pg. 13, claim 1).
Literati Nagy teaches a method of treating a viral disease by administering a PARP inhibitor to a subject (title, abstract).
Collins teaches the administration of a poly(ADP-ribose) polymerase inhibitor for the treatment of a subject against infection by a virus (abstract; Col. 13, claim 1).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to select TLZ nanoparticulate compositions, as taught by Baldwin, to treat a subject with SARS-CoV-2, to arrive at instant claims 1, and 15. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
-Baldwin teaches a method of treating SARS-CoV-2 by administering a pharmaceutical formulation comprising a nanoparticulate delivery vehicle comprising active agents,
-Baldwin exemplifies a nanoparticulate delivery vehicle comprising TLZ,
- Baldwin teaches TLZ as the most potent PARP inhibitor, and
-Hellstrand, Literati-Nagy, and Collins all teach treating viral diseases by administering a PARP inhibitor.
As such, an ordinary skilled artisan would have been motivated to make such a selection, to predictably arrive at an effective method of treating SARS-CoV-2 with a potent PARP inhibitor.
Regarding claims 2-3, and 16-17 Baldwin teaches talazoparib.
Regarding claim 8, Baldwin teaches a composition.
Regarding claim 9, Baldwin teaches a kit (pg. 20, claims 16, 17, 21, 22), and additional anti-viral drugs ([0019], [0091], pg. 13-Table 2).
Allowable Subject Matter
Claim 7 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN WELLS whose telephone number is (571)272-7316. The examiner can normally be reached M-F 7:00-4:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James (Jim) Alstrum-Acevedo can be reached on 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LAUREN WELLS/Examiner, Art Unit 1622