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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 4/13/2026 has been entered.
Claims 1-15 stand cancelled. Claims 28-39 were newly added. Claims 16 and 27 were amended. Claims 16-39 are pending and under consideration.
Foreign Priority
Applicant’s claim for the benefit under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) to EP 20000170.9 filed 4/27/2020 and EP 20000172.5 filed 4/28/2020 is acknowledged.
Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed foreign applications EP 20000170.9 and EP 20000172.5, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
The EP Applications lack support for:
nose spray (claim 26 and 38) – the applications discuss sprays in general and nasal application generically, and discuss pharyngeal application via throat spray, but there is no support for a “nose spray”.
Consequently, the effective filing date of claims 26 and 38 is 4/26/2021. The remainder of the claims are afforded the effectively filed date of 4/27/2020.
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)(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 16-17, 19-21, 23-24, 26, 28-29, 31-33, 35-36, and 38 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Cohen et al. (WO 2021/216759, published 10/28/2021, effectively filed 4/21/2020 which predates the earliest instant foreign priority claim of 4/27/2020).
Cohen et al. teach the treatment (relevant to claims 16-17, 19-21, 23-24, 26) or prevention (relevant to claims 28-29, 31-33, 35-36, and 38) of SARS-CoV-2 infection with quinine, preferably quinine sulphate dihydrate, which is preferably delivered via a nasal delivery device, such as an inhaler, atomizer or nebulizer (claims 16-17, 19-21, 23-24), e.g. a vibrating mesh nebulizer (p. 21, I. 13 - p. 22, I. 27). No other actives are administered so Cohen et al. teaches quinine as monotherapy. The compositions can be in the form of a liquid and/or aerosol (p. 9, I. 20-24) or as a dry powder for oral drug delivery (p. 17, lines 26-27). It is shown that quinine is effective in reducing SARS-CoV-2 infection in sinonasal ALI (air-liquid interface) (p. 26, I. 15 - p. 27, I. 24). Nasal instillation of a 0.1 % (1 mg/ml) solution of quinine sulfate dihydrate in saline protects ferrets against SARS-CoV-2 infection (p. 28, I. 25 - p. 30, I. 15, which includes nose spray). The human clinical trial NCT04408183 is described (p. 30, I. 16 - p. 31, I. 5).
Regarding the claim limitation that treatment is by inhibiting the SARS-CoV-2 replication, Cohen et al. is silent on this effect. However, as Cohen et al. teaches administering quinine to treat and prevent SARS-CoV-2, which is the sole required active step of the claims, it only follows that the quinine would have the same effect claimed (i.e. inhibiting replication).
Response to Arguments
Applicant’s arguments regarding the rejection of claims over Cohen have been fully considered but are not persuasive. Applicant argues that Cohen is a US provisional – it is not. It is a WIPO publication with an effectively filed date of 4/21/2020, which is the date of the provisional the application claims benefit to.
Applicant argues that the provisional application that Cohen claims priority to is not enabled as it uses the future tense to describe the experiments. This argument is not persuasive. See MPEP 2154.01(b) which discusses the effective filing date of references that qualify as prior art under 35 USC 102(a)(2) – which Cohen does.
AIA 35 U.S.C. 102(d) requires that a prior-filed application to which a priority or benefit claim is made must describe the subject matter from the U.S. patent document relied upon in a rejection. However, AIA 35 U.S.C. 102(d) does not require that this description meet the enablement requirements of 35 U.S.C. 112(a). As discussed previously with respect to AIA 35 U.S.C. 102(a)(1), the Office does not view the AIA as changing the extent to which a claimed invention must be described for a prior art document to anticipate the claimed invention under AIA 35 U.S.C. 102.
Thus enablement does not factor in to the effectively filed date of the Cohen reference.
To the extent that applicant may argue that MPEP 2154.01(b) is incorrect, the examiner notes that prophetic examples can be enabling. The provisional application clearly shows someone how to make and use quinine to treat and prevent SARS-CoV-2 without undue experimentation.
Applicant also argues that the application is novel over Cohen as Cohen describes how quinine might work by stimulating the innate immune system (arguments p. 9). Applicant argues nothing in Cohen shows or suggests quinine has an effect on the replication of SARS-CoV-2 itself. This argument is not persuasive. As addressed in the rejection Cohen teaches administering the same compound to the same patient population claimed (those having SARS-CoV-2 in claims 16+; and those at risk of contracting SARS-CoV-2 in claims 28+) in the same formulations claimed. There can be no other outcome. There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003) – MPEP 2112.
It may be true that applicant discovered that quinine inhibits SARS-CoV-2 replication. But that is not patentable as Cohen already taught administering quinine for the exact same purpose. "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). MPEP 2112.
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.
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 16-39 are rejected under 35 U.S.C. 103 as being unpatentable over Charous (WO 03/039546, IDS) in view of Peralta et al. (US 2020/0237689, filed 3/24/2020).
Charous teaches the treatment or prevention of viral respiratory infections, including human corona virus infection (Summary of the invention p. 7), by administering an anti-malarial compound in a targeted fashion to the organ that is infected, preferably quinine or quinidine among a number of derivatives (p.1 Field of the Invention, p. 13). The anti-malarials quinine and quinidine are both taught to have antiviral activity alone which reads on the claim limitation of monotherapy. Administration can be via inhalation, e.g. in the form of aerosols, powders or mists, which can be administered by a vibrating ultrasonic nebulizer; in liquid particulate forms, as nasal spray, eye drops or oral pastes (page 18, lines 1-9; page 8, lines 17-19; page 13, lines 6-8; page 23, lines 9-23; page 24, lines 1-4; page 25, line 28 - page 26, paragraph 4; page 27, lines 3-17; page 29, line 27 - page 30, line 2; page 31, lines 15-18). Administration is to the nasopharynx and bronchial airway for respiratory viruses (p. 2 final paragraph, p. 7 Summary of the Invention). Charous also teaches that oral administration of anti-malarials is well known but that the concentration of the drug that reaches the infected organ is less (p. 9, lines 10-11). Targeted administration is preferred but oral is conventional and less effective (note Charous does not say oral is not effective at all (p. 11, lines 24-30). Charous teaches for prophylaxis the anti-malarial compounds are typically delivered in an amount of 2-5 mg/day (p. 25). Note the above 112(b) regarding whether or not prophylaxis patients are included or excluded from the claim scope. Either way, Charous teaches both treatment and prophylaxis.
The teachings of Charous differ from the instant claims in that Charous teaches administering quinine and quinidine for the treatment of viruses including human corona virus among others, but fails to teach the specific human corona virus which is SARS-CoV-2. Charous also teaches several forms of administration but does not teach sublingual (claim 22).
Peralta et al. teach that coronaviruses are a group of related viruses that cause respiratory tract infections – included in this family is SARS-CoV-2 and various other human coronaviruses ([0004], [0206]). Peralta et al. also teaches forms of topical delivery is sublingual, respiratory or nasal ([0252]).
It would have been prima facie obvious to one of ordinary skill in the art before the time of filing to have administered the antiviral quinine or quinidine compositions of Charous to treat SARS-CoV-2 with a reasonable expectation of success. One would have been motivated to do so as Charous teaches that quinine and quinidine are antiviral against human corona viruses – especially when delivery is targeted to the site of infection. SARS-CoV-2 falls under the family of human corona viruses and is known to cause respiratory tract infections – so there is motivation to target delivery to the respiratory system. Peralta et al. also teaches that sublingual, respiratory and nasal administration are all topical forms of administration so it would have been obvious to have used these forms of administration interchangeably.
Regarding the claim limitation that treatment is by inhibiting the SARS-CoV-2 replication, the teachings of Charous and Peralta et al. render obvious administering quinine and quinidine to treat and prevent SARS-CoV-2, which is the sole required active step of the claims. As a result on would be imbued with a reasonable expectation that the quinine and quinidine would individually have the same effect claimed (i.e. inhibiting replication).
Response to Arguments
Applicants arguments regarding the rejection of all claims over Charous in view of Peralta have been fully considered but are not persuasive.
Applicant argues quinine is not among the preferred actives discussed by Charous. This is simply not true. Page 13 states, “An especially preferred class of anti-malarials has a core quinoline structure (examples are mefloquinine and quinine) which is usually substituted at one or more positions, typically at least at the 4- and/or 8-positions. Quinine and it’s 4- and/or 8- substituted derivatives are taught to be a preferred class of drugs. Regarding quinidine, Charous teaches on p. 18 that another preferred class of anti-malarials are the cinchona alkaloids of the generic structure shown at the top of p. 18 and which include both quinine and quinidine.
Applicant argues that Charous pre-dates SARS-CoV-2 and treatment of the “seasonal coronaviruses” of Charous would not reasonably provide an expectation that SARS-CoV-2 could be treated. Applicant argues that “seasonal coronaviruses” are more mild. Applicant points to several references pre- and post-SARS-CoV-2 to argue the binding domains of coronaviruses differ and various drugs (nucleocapsid, RNA polymerase inhibitors, etc., arguments pp. 11-12). Applicant concludes that broad-spectrum coronavirus inhibitors require highly conserved targets. Applicant points to a number of references discussing typical drugs for SARS-CoV-2 including nirmatrelivir, remdesivir, molnupiravir, see pp.12-13.
The argument that coronaviruses in general are seasonal and weaker than SARS-CoV-2 is not supported by evidence. Arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) and In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). MPEP 716.01(c). The references proving arguments that various coronaviruses have different binding domains does not somehow suggest that the teachings of Charous are not relevant. The fact remains that Charous teaches that anti-malarials including quinine and quinidine are preferred and effective treatments for coronaviruses. Peralta shows that SARS-CoV-2 is a coronavirus. Applicant has provided no evidence suggesting that quinine and quinidine perform unexpectedly better than other anti-malarials against SARS-CoV-2. In order to show unexpected results applicant needs to provide a comparison to the closest prior art (here Charous).
Applicant argues chloroquine and hydroxychloroquine which are structurally related to quinine and quinidine (the examiner agrees and Charous also teaches as much) show effects against seasonal coronaviruses but have poor effect against SARS-CoV-2 and are usually not used anymore. Applicant argues there would have been no reason to use the structurally related quinine and quinidine. Again this argument is mere attorney argument and not supported. Objective evidence showing quinine and quinidine unexpectedly out perform hydroxychloroquine and chloroquine against SARS-CoV-2 could be persuasive in overcome the obviousness rejection.
Conclusion
Claims 16-39 are rejected. No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kortney Klinkel, whose telephone number is (571)270-5239. The examiner can normally be reached on Monday-Friday 10 am to 7 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jennifer Michener can be reached on 571-272-14241424. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627
