NON-FINAL REJECTION
This application is a 35 U.S.C. 371 (national stage) application of PCT/EP2021/077773, filed Oct. 7, 2021, which claims benefit of foreign priority to EP 20306165.0, filed Oct. 7, 2020.
Claims 16-34, as amended, are pending.
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
Acknowledgment is made of applicant's claim to foreign priority under 35 U.S.C. 119(a)-(d).
Information Disclosure Statement
The information disclosure statements (IDS) submitted on Jun. 28, 2023 and Nov. 4, 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group I, drawn to methods of treating COVID-19 by administering an EP2 and/or EP4 receptor agonist; and taprenepag as the species of EP2 and/or EP4 agonist, in the reply filed on Nov. 4, 2025 is acknowledged.
Claims 31-32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention there being no allowable generic or linking claim. Election was made without traverse in the reply filed on Nov. 4, 2025.
Claims 16-30, 33, and 34 are currently pending and under consideration.
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 (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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 16-18, 21-30, 33, and 34 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Guilford et al. (US Pub. 2015/0196578), in view of Tsuji (FEBS Open Bio (10) 995–1004 (May 29, 2020)) (both cited on PTO-892).
Guilford et al. disclose that a combination of an EP4 receptor agonist and certain antiviral agents work synergistically to treat viral diseases that induce a cytokine storm; i.e., treatment of a viral disease with an EP4 receptor agonist in combination with an antiviral agent results in significant, greater-than-additive increases in survival compared to treatment with either drug alone (para. [0011]).
Specifically, Guilford et al. claim methods for treating a viral disease comprising administering to a human patient in need thereof an antiviral agent in combination with an EP4 receptor agonist, e.g., evatanepag (CP-533536), having the structural formula,
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(claims 1, 8, and 18), wherein the viral disease is caused by a coronavirus, such as a virus that causes severe acute respiratory syndrome (SARS) (claim 7; para. [0012]).
Guilford et al. disclose and claim methods for treating a coronavirus infection comprising administering to a human patient in need thereof an EP4 receptor agonist, e.g., evatanepag, further in combination with an antiviral agent, as recited by claim 30.
Guilford et al. differs from independent claim 16 in that the species of coronavirus, SARS-CoV-2 which causes COVID-19, is not specified.
However, Tsuji identifies evatanepag as a drug candidate for treating COVID-19 with high binding affinity to the main SARS-CoV-2 coronavirus protease (Mpro) (abstract; Table 1).
Therefore, it would have been predictable to one of ordinary skill in the art as of the filing date to administer evatanepag to treat COVID-19, as recited by claims 16-18, with a reasonable expectation of success, because Guilford et al. disclose and claim methods for treating a coronavirus infection comprising administering a therapeutically effective amount of evatanepag, and Tsuji identifies evatanepag as having high binding affinity to the main SARS-CoV-2 coronavirus protease (Mpro), the coronavirus species that causes COVID-19.
The rationale to combine the cited references is premised on the findings that (1) the prior art includes each ele-ment claimed, with the only difference between the claimed invention and the prior art being the lack of actual combination of the elements in a single prior art reference; (2) one of ordinary skill in the art could have combined the elements as claimed by known methods, and that in combination, each ele-ment merely performs the same function as it does separately; and (3) one of ordinary skill in the art would have recognized that the results of the combi-nation were predictable.
As evidenced by the instant specification ("Background of Invention," p. 2, lines 4-23):
the majority of COVID-19 patients experience mild or moderate symptoms, as recited by claim 24;
up to 25% of people around the world have at least one underlying condition that put them at increased risk of severe COVID-19, as recited by claim 25;
some subjects develop a severe form of COVID-19 that may lead to acute respiratory failure. Complications of COVID-19 also include thrombotic complications, pulmonary embolism, cardiovascular failure, renal failure, liver failure and secondary infections, as recited by claims 26 and 27;
disease severity is tightly associated with age and the presence of comorbidities, in particular, mortality rates are above 15% for the elderly (over 80 years of age), as recited by claim 28; and
COVID-19 patients with a low IFN-gamma response during the early stage of illness is associated with severe disease and complications, due to a massive cytokine storm, as recited by claim 29.
As further evidenced by the instant specification (p. 2, lines 5-9), COVID-19 generally presents first with symptoms including headache, muscle pain, fatigue, fever and respiratory symptoms (such as a dry cough, shortness of breath, and/or chest tightness).
Therefore, it would have been predictable to an ordinarily skilled clinician to diagnose SARS-CoV-2 infection and initiate treatment as soon as possible following the onset of symptoms, e.g., within less than 6 days, as recited by claims 21-23, with a reasonable expectation of success, in order to reduce the risk of disease progression and achieve the earliest treatment response.
The cited references do not explicitly disclose that administering a therapeutically effective amount of an EP2 and/or EP4 agonist to a subject suffering from COVID-19 regulates interferon signaling pathway, as recited by claim 33, or induces one or more of IFIT1, IFIT2 and IFIT3 genes in the subject, as recited by claim 34.
However, these are intrinsic effects every time an EP2 and/or EP4 agonist is administered to a subject with COVID-19, whether or not they were recognized or appreciated.
Claims 33-34 are drawn to the result of administering an EP2 and/or EP4 agonist to treat COVID-19. While the references do not explicitly recognize those results, their discovery is tantamount only to finding a new property intrinsic in carrying out an old method. Because Guilford et al. and Tsuji disclose methods of administering the same compounds to treat the same conditions in the same patient population, the results of the claimed methods are intrinsic in the methods disclosed, taught, and suggested by the cited references.
Claims 16-30, 33, and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Guilford et al. (US Pub. 2015/0196578), in view of Tsuji (FEBS Open Bio (10) 995–1004 (May 29, 2020)) as applied to claims 16-18, 21-30, 33, and 34 above, and further in view of Lebender et al. (Pulm. Pharm. Therap. (49) 75-87 (2018)); and Torres et al. (WO2014/206808) (all cited on PTO-892).
As discussed above, Guilford et al. and Tsuji disclose, teach, and suggest methods for treating the coronavirus infection COVID-19 comprising administering to a human patient in need thereof an EP4 receptor agonist, e.g., evatanepag (CP-533536).
Lebender et al. disclose that the advent of potent and selective EP receptor agonists and antagonists has important implications for lung health and disease, as PGE2-mediated EP receptor activation affects migration of airway smooth muscle cells, airway microvascular leak, tone regulation of pulmonary blood vessels, mast cell degranulation, bronchodilation, cough, angiogenesis and airway inflammation, etc. (abstract).
In particular, selective EP receptor agonists are potential novel therapeutics to combat chronic respiratory diseases and lung conditions (p. 75, right col.). In particular, Lebender et al. disclose the selective EP2 agonists CP-533536 (evatanepag) and CP-544326 (taprenepag) (p. 79, left col.), shown side-by-side below for comparison:
Taprenepag (CP-544326)
Evatanepag (CP-533536)
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Binding affinity for EP2 receptor
Ki = 10 nM
Binding affinity for EP2 receptor
Ki = 50 nM
Given the close structural similarity of the two compounds, differing only at the phenyl para-substituent (tert-butyl in evatanepag vs. pyrazole in taprenepag), and their common activity as potent selective EP2 agonists, a skilled artisan would have considered these two compounds interchangeable equivalents in methods of treating respiratory illnesses.
This interchangeability is further evidenced by, e.g., Torres et al., which discloses both evatanepag and taprenepag isopropyl as EP2 receptor agonists for treating respiratory conditions such as asthma (claims 6 and 13).
Therefore, it would have been predictable to one of ordinary skill in the art as of the filing date to administer taprenepag to treat COVID-19, as recited by claims 16-20, with a reasonable expectation of success, because Lebender et al. and Torres et al. disclose both taprenepag and evatanepag as highly selective EP2 agonists useful for treating respiratory conditions involving, e.g., cough and airway inflammation.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARA E. TOWNSLEY whose telephone number is 571-270-7672. The examiner can normally be reached on Mon-Fri from 9:00 am to 6:00 pm (EST). If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jeff S. Lundgren, can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARA ELIZABETH TOWNSLEY/Examiner, Art Unit 1629