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 .
Receipt is acknowledged of Amendments, Remarks and an IDS filed on 10/24/25. Claims 1, 27 and withdrawn claim 62 have been amended, claims 2-3, 60 and 100 have been cancelled and no new claims have been added. Accordingly, claims 1, 4-16, 27, 63, 70 and 77 are under examination on the merits. Claims 17-26 and 62 are withdrawn.
Rejections and/or objections not reiterated from the previous Office Action are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Applicant’s claims:
Claim 1 is drawn to a method for reducing viral respiratory infection in a subject in need thereof, the method comprising: administering a formulation intranasally or by inhalation to the subject having a viral respiratory infection, wherein the viral respiratory infection is coronavirus or SARS-CoV-2, wherein the formulation comprises a therapeutically effective amount of a statin; and a pharmaceutically acceptable carrier.
Claim interpretation:
Applicants recite in the Specification that “The virus, SARS-CoV-2, can cause serious pulmonary complications, including severe respiratory failure, acute lung injury (ALI), Acute Respiratory Distress Syndrome (ARDS), pneumonia, sepsis, blood clots, and death, but in many cases is asymptomatic. The disease caused by the virus is known as COVID-19” (See published spec at [0003]). Applicant also disclose that “Non-limiting exemplary viral respiratory infections include pulmonary infections by coronaviruses (including, for example, SARS-CoV, MERS-CoV, and SARS-CoV-2)” (See [0084).
Thus, according to the Specification, SARS-CoV-2 and coronavirus are the virus, while COVID 19 is the disease caused by this virus. However, the virus and disease appear to be used interchangeably. Claims 4, 63, 70 and 77 refer to treating a SARS-CoV-2 and COVID-19.
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, 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.
Claims 1, 4-8, 10-12, 27, 63, 70 and 77 are rejected under 35 U.S.C. 103 as being unpatentable over Prendergast (US 20090318379) in combination with European Heart Journal - Cardiovascular Pharmacotherapy (Statin therapy in COVID-19 infection) (Provided in IDS filed on 06/28/23).
Prendergast teaches methods for the treatment of viral influenza using statins, or pharmaceutically effective salts, including mevastatin, lovastatin, pravastatin and simvastatin (See abstract, [0018], [0034] and claim 4).
Routes of administration include administration via oral or nasal inhalation, and may be delivered using a mechanical form including, an inhaler or a nebuliser device (See [0081]-[0083]).
The said pharmaceutical composition comprises at least one pharmaceutical excipient, diluent or carrier, preferably these are selected according to the intended route of administration (See [0043]).
Claim 1 is directed to a method for the treatment and/or prophylaxis of Influenza type A infection, the method comprising the steps of: providing a composition comprising at least one statin or an analogue, derivative, metabolite, prodrug or a pharmaceutically acceptable salt thereof, and administering a therapeutically effective amount of said composition to a subject in need of such treatment (See claim 1 and [0020]).
Prendergast teaches treating influenza viral infections but is silent regarding other viral infections including SARS-CoV-2 or coronavirus or COVID-2. This would have been obvious in view of the disclosure by European Heart Journal.
European Heart Journal teaches that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of the current pandemic of coronavirus disease 2019 (COVID-19). It is disclosed that “In this paper we support the rationale for the use of statins, a class of drugs with widespread availability and an optimal tolerability profile, as an add-on treatment for COVID-19 patients, on the basis of their known immunomodulatory properties” (See 1st col. 1st para).
It is stated that statins have also been evaluated as an immunomodulatory treatment in various infectious diseases, including influenza (See 2nd col. 1st para) and that similar to avian influenza viruses, beta-coronaviruses cause severe respiratory illnesses by triggering an intense proinflammatory host response. Some immunomodulatory therapies have indeed proven beneficial in patients with SARS, MERS, and COVID-19 (See 2nd col., 2nd para).
It is further disclosed that “Cardioprotective actions of statins should also be taken into consideration in the setting of SARS-CoV-2 infection. Observational studies have found that elderly people with cardiovascular comorbidities are more likely to be infected with SARS-CoV-2 and to develop severe symptoms. In addition, there is evidence of direct cardiovascular involvement in some cases of COVID-19. Furthermore, the lipid-lowering action of statins could treat the hyperlipidaemia associated with the use of protease inhibitor-based antiretroviral and immunosuppressive drugs in COVID-19 infection (See 3rd Col. 2nd para).
It is concluded that treatment with statins improves the clinical course of patients with COVID-19 (See page 2).
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of European Heart Journal with that of Prendergast to arrive at the instant invention. It would have been obvious to do so because Prendergast teach a method of treating influenza viral infections in a subject by administration to the subject’s pulmonary system (i.e by inhalation) a formulation comprising a statin including simvastatin and a carrier. While Prendergast is silent with regard to treating other respiratory viral infections including those caused by SARS-CoV-2 or coronavirus, European Heart Association teaches that statins are indeed effective in treating COVID-19 infections and that treatment with statins improves the clinical course of patients with COVID-19. European Heart Association also details the effects and benefits of statins in treating patients. As such one of ordinary skill in the art would have been motivated to have incorporated the teachings of European Heart Association in the formulations and methods of Prendergast and arrive at a method of treating respiratory viral infections including COVID-19 by inhalation of a composition comprising statins such as simvastatin to the subject in need of such treatments with a reasonable expectation of success.
The claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
Claims 13-16 are rejected under 35 U.S.C. 103 as being unpatentable over Prendergast (US 20090318379) in combination with European Heart Journal - Cardiovascular Pharmacotherapy (Statin therapy in COVID-19 infection) (Provided in IDS filed on 06/28/23) as applied to claim 1 above and in further view of Tulbah et al (Biological effects of simvastatin formulated as pMDI on pulmonary epithelial cells) (Provided in IDS filed on 07/07/25).
Prendergast’s teachings are delineated above and incorporated herein.
Prendergast teaches treating influenza viral infections with a composition comprising a therapeutically effective amount of a statin including simvastatin but is silent regarding the amount. This would have been obvious in view of the disclosure by Tulbah et al.
Tulbah et al disclose a study performed aimed at evaluating the biological effects of Calu-3 epithelial cells in response to the delivery of simvastatin (SV) via solution pressurized metered dose inhaler (pMDI), and state that “It was found that SV had the ability to penetrate into the respiratory epithelium and convert into its active SV hydroxy acid (SVA) metabolite. Furthermore, the amount of mucus produced was significantly reduced when SV was deposited on Calu-3 compared to untreated cells. Additionally, SV delivered by pMDI reduces production of IL-6, 8 and TNF-α from Calu-3 following stimulation with lipopolysaccharide (LPS). SV also showed equivalent antioxidant property to vitamin E” (See Page 92, Abstract and Methods).
Tulbah et al also disclose a preparation of the pressurised metered dose (pMDI) SV solution formulation comprising 6% (w/w) ethanol and 0.25% (w/w) SV weighed directly into an aluminium canister to obtain a final dose of 150 μg per actuation (See Page 94, 1st col. 2nd para).
Tulbah et al conclude that the aerosols of SV produced from a pMDI solution formulation were shown to be able to penetrate across the Calu-3 epithelial cells and convert into its active SVA metabolite. In addition, the SV pMDI formulation did not induce any inflammation or oxidative stress upon deposition onto the Calu-3 epithelial cells. The observed inhibitory effects of SV pMDI on mucus production, inflammatory mediators and oxidative stress support the role of SV as immune-modulatory agent that could potentially be used in the management of chronic respiratory diseases. Future studies will be focusing on identifying the mechanism of SV transport and correlating the results to in vivo studies (See Page 100, conclusion).
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Tulbah et al with that of Prendergast to arrive at the instant invention. It would have been obvious to do so because Prendergast teach a method of treating influenza viral infections in a subject by administration to the subject’s pulmonary system (i.e by inhalation) a formulation comprising a statin including simvastatin and a carrier. While Prendergast is silent with regard to the dosage amount, Tulbah et al teaches that a pressurized solution of simvastatin has biological effects on pulmonary epithelial cells. Tulnah et al disclose a solution formulation prepared for administration by inhalation to the subjects and disclose that the dose is about 150 µg per actuation. As such one of ordinary skill in the art wishing to follow the teachings of Prendergast would have been motivated to have looked in the art for better guidance on the dosage amount, as taught by Tulbah et al with a reasonable expectation of success.
The claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Prendergast (US 20090318379) in combination with European Heart Journal - Cardiovascular Pharmacotherapy (Statin therapy in COVID-19 infection) (Provided in IDS filed on 06/28/23) as applied to claim 1 above and in further view of Cruz de Oliveira et al (Evaluation of the preference, satisfaction and correct use of Breezhaler® and Respimat® inhalers in patients with chronic obstructive pulmonary disease- INHALATOR study) (Respiratory Medicine).
The teachings of Prendergast are delineated above and incorporated herein.
Prendergast teaches inhalable formulations comprising a statin including simvastatin and a carrier delivered via a mechanical inhaler including a nebulizer or pressurized inhaler. However, Prendergast is silent regarding the claimed commercially available inhalers of claim 9. This would have been obvious in view of the prior art including Cruz de Oliveira et al.
Cruz de Oliveira et al teach disclose an evaluation of the preference, satisfaction and correct use of Breezhaler® and Respimat® inhalers in patients with COPD. According to the Feeling of Satisfaction with Inhaler Questionnaire - FSI 10 patients were more satisfied using Breezhaler® than Respimat® and 57.1% preferred using Breezhaler® (p = 0.001) while 30.1% preferred Respimat® (p < 0.001) (See Title and Abstract).
It is concluded that patients with COPD in Brazil showed a greater preference and satisfaction with Breezhaler® over Respimat® (See Conclusion, page 66).
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Cruz de Oliveira et al with that of Prendergast to arrive at the instant invention. It would have been obvious to do so because Prendergast teach a method of treating influenza viral infections in a subject by administration to the subject’s pulmonary system (i.e by inhalation) a formulation comprising a statin including simvastatin and a carrier. Prendergast teach that the said formulation may be administered to the subject by way of a mechanical inhaler such as nebulizer or pressurized inhalers. While Prendergast is silent with regard to the commercially available inhaler devices, such inhalers are well known and commonly used in the art and industry. Cruz de Oliveira et al teach that such devices are in use and that one may be preferred to the other.
Thus, one of ordinary skill in the art wishing to follow the teachings of Prendergast would have been motivated to have looked in the art for available inhaler devices to deliver the said formulations with, as taught by Cruz de Oliveira et al.
The claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
The claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
Response to Arguments
Applicant's arguments filed 10/24/25 have been fully considered but they are not persuasive.
Applicant’s amendments to the claims have necessitated modified grounds of rejections. Applicant’s arguments so far as they pertain to the maintained references and rejections are discussed below.
Applicant argues that Pendergast in combination with European Heart Journal (Castiglione et al), does not teach the claimed methods. Applicant tabulated the recitations of the claims and each of the references (See pages 9-10) and argue that Pendergast focuses on a hypothetical rat model of H3N2 influenza… and does not describe a viral respiratory infection that is coronavirus or SARS-CoV-2. Applicant also argues that “Castiglione et al merely sets out a hypothesis for using a statin to treat COVID-19 and concludes that certain forms of statin therapy could improve the clinical course of patients with COVID-19” (See remarks, page 10).
The arguments have been fully considered but found unpersuasive. Regarding the argument that Pendergast focuses on a hypothetical rat model, it is noted that Pendergast specifically teaches, discloses and claims “A method for the treatment and/or prophylaxis of Influenza type A infection, the method comprising the steps of: providing a composition comprising at least one statin or an analogue, derivative, metabolite, prodrug or a pharmaceutically acceptable salt thereof, and administering a therapeutically effective amount of said composition to a subject in need of such treatment” (See claim 1). Applicant provides no evidence that Pendergast focuses on a hypothesis.
Regarding the argument that Pendergast only focuses on rats and canine, it is noted that Pendergast very clearly discloses treating “subjects” which are defined as mammal’s including humans (See at least [0018], [0077] and claims).
Regarding the argument that Pendergast does not teach treating coronavirus or SARS-CoV-2, it is noted that this missing limitation is taught by European Heart Journal. Pendergast teach treating or reducing the effects or severity of a viral infection such as influenza infection by nasal or inhalation administration of a composition comprising a statin including simvastatin. The only difference between claimed methods and the teachings of Pendergast is that the viral infection is (caused by) coronavirus or SARS0CoV-2. European Heart Journal article clearly discloses and motivates one of ordinary skill in the art to also administer a formulation comprising a statin to a patient suffering from or at risk of a viral infection caused by COVID-19.
Applicant also argues that Castiglione et al (European Heart Journal) focuses on avian influenza, seasonal influenza and Ebola and that neither the Office nor Castiglione et al provide data or evidence that such treatment provides an effective treatment of coronavirus, SARS-CoV-2 or COVID-19 (See remarks, page 10).
The above argument is also unpersuasive. It is noted that the title of the article is “Statin therapy in COVID-19 infection” and as Applicants reproduced the conclusion above, it is clearly disclosed that statin therapy is found beneficial and effective in treating COVID-19. While it is noted that a reference is not required to show data to render a method or a claim obvious, European Heart Journal actually provides evidence. At least in Column 3, the article discloses the impact of statins on infections in terms of inflammatory pathways, inhibition of NF-B etc. It is actually stated that based on this evidence, the use of a statin as an immunomodulatory treatment for COVID-19 patients may deserve considerations. The article further discloses the molecular mechanism of actions and proposed advantages of statins in COVID-19 in figure 1 (See page 2) and state that “through these mechanisms, statins may prove beneficial in COVID-19.
It is further noted that the entire article is teaching the effects of statins on SARS-CoV-2 and COVID-19, but also mentions avian influenza and Ebola. In this regard, the courts have held that "It is impermissible within the framework of section 103 to pick and choose from any one reference only so much of it as will support a given position, to the exclusion of the other parts necessary to the full appreciation of what such reference fairly suggests to one of ordinary skill in the art." In re Wesslau, 353 F.2d 238, 241 (C.C.P.A. 1965); see also Bausch & Lomb, Inc. v. Barnes-Hind/Hydrocurve, Inc., 796 F.2d 443,448-49 (Fed. Cir. 1986).
Next argument is that Castiglione et al does not teach intranasal administration (See remarks, page 11).
The above argument is also not found convincing. As stated above, the method of reducing or treating a viral infection by administering a formulation comprising a statin via nasal or oral inhalation is taught by Pendergast. Castiglione et al was relied upon for teaching treating viral infections including COVID-19. In this regard the courts have held that "The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference.... Rather, the test is what the combined teachings of those references would have suggested to those of ordinary skill in the art." In re Keller, 642 F.2d 413, 425, 208 USPQ 871, 881 (CCPA 1981). See also In re Sneed, 710 F.2d 1544, 1550, 218 USPQ 385, 389 (Fed. Cir. 1983) ("[I]t is not necessary that the inventions of the references be physically combinable to render obvious the invention under review."); and In re Nievelt, 482 F.2d 965, 179 USPQ 224, 226 (CCPA 1973) ("Combining the teachings of references does not involve an ability to combine their specific structures.").
Applicant further argues that “there is no disclosure in Prendergast or Castiglione et al. of the treatment effect of a statin on a coronavirus or SARS-CoV-2 viral respiratory infection or virus infection. Thus, the skilled person would have no expectation of success of an effective therapy based on the disclosure in the cited art. The additional feature of claims 27 and 70, that the subject may be exposed to the viral infection, is even further removed from the cited art” (See remarks, pages 12-13).
The above argument is not convincing either. As clearly shown by the rejections above, Pendergast teaches “The present inventor has surprisingly found that the administration of the active metabolite of a statin …. to a patient at specified dosages, by any route of administration, but preferable by nasal administration, will confer infection resistance to influenza virus challenge. …. the statin metabolite compound functions to prevent influenza virus attachment and infection to the nasal/thoracic epithelial cells to which the influenza virus has specific affinity for. This therapeutic approach has utility in preventing influenza infection by strains of Influenza A which result from virus reassortment” (See [0019]).
Pendergast also teaches “As used herein, the term “therapeutically effective amount” means the amount of a compound or composition which is required to reduce the severity of and/or ameliorate influenza A viral infection, or at least one symptom thereof, or which serves to prevent the progression of influenza A infection or the development of one or more of the symptoms associated with mucositis” (See [0073]).
Pendergast further discloses that “therapeutic and prophylactic treatments include amelioration of the symptoms of a particular condition or preventing or otherwise reducing the risk of developing a particular condition” (See [0080).
Castiglione et al also teaches the benefits and effects of statins on treating COVID-19 infections.
Applicant argues that neither Pendergast nor Tulbah describe the use of statins to reduce coronavirus or SARS-CoV-2 viral infection (See remarks, page 13).
This argument is similarly unpersuasive. As stated above, Pendergast teaches administration of statins to a patient via nasal or oral inhalation. European Heart Journal teaches administration of statins for treating COVID-19 and SARS-CoV-2 viral infections and Tulbah et al teach delivery of simvastatin (SV) via solution pressurized metered dose inhaler (pMDI), and state that simvastatin is administered at a final dose of 150 μg per actuation. Thus, Tulbah et al provide guidance on the dosage amount of statin for inhalation.
Regarding the rejection of claim 9 over the references, Applicant argues that Cruz de Oliveira et al do not teach all the limitations of claims 1 and 9 (See remarks, page 14).
This argument is also not persuasive because Cruz de Oliveira et al was relied upon for its disclosure of commercially available inhaler devices as claimed in claim 9. Thus, the combination of references meet all the claimed limitations.
In conclusion,
From the combined teaching of the cited references, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Claims 1, 4-16, 27, 63, 70 and 77 are rejected. Claims 17-26 and 62 are withdrawn.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/Mina Haghighatian/
Mina Haghighatian
Primary Examiner
Art Unit 1616