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 .
Priority
This application is a national stage entry of PCT/EP2021/070272 filed on 07/20/2021. Acknowledgment is made of applicant's claim for foreign priority based on applications filed in Europe on 07/20/2020 and 12/18/2020. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-11 and 15, drawn to a method of treatment of a viral infection comprising administering a PDE3-inhibitor; enoximone as a species of a PDE3-inhibitor; and respiratory viral infection of claim 5 as a species a viral infection in the reply filed on November 28, 2025 is acknowledged.
Claims 3, 4 and 12-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group or species, there being no allowable generic or linking claim.
Claims 1, 2 and 5-11 are being examined as they read on the elected species.
Claim Rejections - 35 USC § 112
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.
Claim 5, 7, 8 and 11 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.
Regarding claims 5 and 7, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claims 7, 8 and 11, the word "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 7, the phrase "more preferably" or “most preferably” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 5 recites the broad recitation a respiratory viral infection, and the claim also recites an infection by human respiratory syncytial virus which is the narrower statement of the range/limitation.
Claim 11 recites the broad recitation at least once per day, and the claim also recites at least twice per day or three times per day which is the narrower statement of the range/limitation.
Claim 8 recites the broad recitation exhaustion, and the claim also recites an COVID-19-associated exhaustion which is the narrower statement of the range/limitation.
Claim 7 line ii recites the broad recitation pulmonary edema, and the claim also recites pulmonary edema that is resistant to corticosteroids, to adrenaline, or to both, which is the narrower statement of the range/limitation.
Claim 7 line iii recites the broad recitation outside of the lungs, and the claim also recites in the gut or of the skin, which is the narrower statement of the range/limitation.
Claim 7 line vi recites the broad recitation inflammation, and the claim also recites inflammation in the lungs and/or airways which is the narrower statement of the range/limitation.
Claim 7 line vii recites the broad recitation an age of at least 35, and the claim also recites more preferably at least 50, even more preferably at least 60, still more preferably at least 65, most preferably at least 70 which is the narrower statement of the range/limitation.
Claim 7 line xii recites the broad recitation with or without evidence of thromboembolic events and/or without evidence of vascular leakage, and the claim also recites without evidence of thromboembolic events and/or without evidence of vascular leakage which is the narrower statement of the range/limitation.
Claim 7 line xiii recites the broad recitation viral infection, and the claim also recites COVID-19 which is the narrower statement of the range/limitation.
Claim 7 line xvii recites the broad recitation organ function impairment, and the claim also recites renal, hepatic, and/or myocardial impairment which is the narrower statement of the range/limitation.
Claim 7 line xxiii recites the broad recitation any of xiii-xxii, and the claim also recites all of xiii-xv which is the narrower statement of the range/limitation.
Claim 7 line xxviii recites the broad recitation embolism, and the claim also recites pulmonary embolism which is the narrower statement of the range/limitation.
Claim 7 line xxviii recites the broad recitation vascular leakage, and the claim also recites pulmonary vascular leakage which is the narrower statement of the range/limitation.
Claim 7 line xxix recites the broad recitation emphysema, and the claim also recites centrilobular emphysema which is the narrower statement of the range/limitation.
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1 and 6-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Altmeyer et al. U.S. Publication No. 2011/0201665 A1.
Claims 1 and 6-11 of the instant application claim a method of treatment of a viral infection, the method comprising administering a PDE3-inhibitor or a pharmaceutically acceptable salt thereof to a subject in need thereof.
Altmeyer et al. teaches compositions, methods, and kits for treating or preventing a viral infection such as an infection caused by an influenza virus (abstract [0002]).
Altmeyer et al. teaches compositions comprising a combination of a neuraminidase inhibitor and a phosphodiesterase inhibitor [0016]. Altmeyer et al. teaches in one embodiment, the PDE inhibitor is a compound in Table 1 or analogs thereof [0016]. Altmeyer et al. teaches that the compounds may be present in an amount sufficient to treat or prevent a viral infection caused by influenza virus (e.g., by any of the influenza types, subtypes, or strains described therein), wherein the influenza virus may or may not be resistant to oseltamivir, in particular, the influenza virus may be of type A, B, or C, or the influenza virus may be of subtype H1N1 [0016]. The composition may be formulated for administration by any route known in the art such as oral, parenteral (e.g., intravenously or intramuscularly), rectal, determatological, cutaneous, nasal, vaginal, inhalant, skin (patch), ocular, intrathecal, and intracranial [0016].
Altmeyer et al. further teaches a method for treating or preventing an influenza viral infection in a patient comprising administering to the subject an amount of a neuraminidase inhibitor and a PDE inhibitor sufficient to treat or prevent the viral infection in the patient wherein, the PDE inhibitor is a compound in Table 1 or analogs thereof [0017]. In certain embodiments, the neuraminidase inhibitor, PDE inhibitor, and (if present) amantadine or rimantine are administered within 7 days, 1 day, or 1 hour of each other or substantially simultaneously [0017].
Altmeyer et al. further teaches that treating includes one or more of the following: (a) arresting, delaying the onset (i.e., the period prior to clinical manifestation of a disorder) and/or reducing the risk of developing or worsening a disorder; (b) relieving or alleviating at least one symptom of a disorder in a mammal, including for example, hypercalcemia; or (c) relieving or alleviating the intensity and/or duration of a manifestation of a disorder experienced by a mammal including, but not limited to, those which are in response to a given stimulus (e.g., pressure, tissue injury or cold temperature) [0042]- [0045].
Altmeyer et al. teaches methods, compositions, and kits for the administration of an effective amount of a combination including a neuraminidase inhibitor and a PDE inhibitor to treat a viral infection [0061]. The invention features methods for treating or preventing influenza viral infections, using a neuraminidase inhibitor in combination with a PDE inhibitor [0062]-[0063].
Altmeyer et al. teaches that influenza is characterized by fever, headache, tiredness, cough, sore throat, runny or stuffy nose, body aches, and diarrhea and vomiting and complications which can develop from an influenza infection include bacterial pneumonia, dehydration, and worsening of chronic medical conditions, such as congestive heart failure, asthma or diabetes; sinus problems and ear infections can also develop [0064]. Altmeyer et al. teaches that mortality due to influenza infection is often associated with lung inflammation, which can be severe [0065]. Influenza virus can also induce cytokines including interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-alpha in the serum and nasopharyngeal fluid and mortality associated with influenza infection is often due to the ability of the influenza A virus to infect the entire lung and induce high levels of macrophage-derived chemokines and cytokines, which results in infiltration of inflammatory cells and severe hemorrhage [0065].
Altmeyer et al. teaches that the PDE inhibitor is a compound which can inhibit the enzymatic activity of one or more of the subtypes of the enzyme phosphodiesterase (PDE), therefore preventing the inactivation of the intracellular second messengers cAMP or cGMP [0092]. PDE inhibitors may be employed in combination with a neuraminidase to treat an influenza viral infection [0093]. Exemplary PDE inhibitors for use in the invention are shown in Table 1, which includes the PDE3 inhibitor, Enoximone (4-methyl-5-{[4-(methylsulfanyl)phenyl]carbonyl}-2,3-dihydro- 1H-imidazol-2-one) and numerous other compounds that inhibit PDE3 (page 10).
Claims 16-18 of Altmeyer et al. claim a method for treating or preventing a viral infection caused by an influenza virus in a patient, said method comprising administering to said patient a first compound that is a neuraminidase inhibitor and a second compound that is a PDE inhibitor in amounts that together are sufficient to treat or prevent said viral infection in said patient, wherein said PDE inhibitor is a compound in Table 1 or an analog thereof.
Thus the cited claims of the instant application are anticipated since Altmeyer et al. specifically teaches and claims a method of treatment of a viral infection, the method comprising administering a PDE3-inhibitor or a pharmaceutically acceptable salt thereof to a subject in need thereof. Moreover, since Altmeyer et al. specifically teaches the administration of a PDE3 inhibitor as claimed for the treatment of a viral infection, the method of Altmeyer et al. will inherently treat the same symptoms of the viral infection as claimed. Thus claims 7 and 8 of the instant application are rejected.
In addition, since Altmeyer et al. specifically teaches the administration of a PDE3 inhibitor as claimed for the treatment of a viral infection, the same effects as claimed in claim 9 will inherently be achieved. Claim 10 is rejected since Altmeyer et al. does not teach or suggest that the PDE-3 inhibitor is for achieving bronchodilation or for treating an allergic reaction.
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 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.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Altmeyer et al. U.S. Publication No. 2011/0201665 A1 as applied to claims 1 and 6-11 above.
Claim 2 of the instant application claims a method of treatment of a viral infection, the method comprising administering a PDE3-inhibitor or a pharmaceutically acceptable salt thereof to a subject in need thereof, wherein the PDE-3 inhibitor is enoximone.
Altmeyer et al. is as set forth above,
Altmeyer et al. does not specifically exemplify the treatment with the PDE-3 inhibitor enoximone.
However, Altmeyer et al. teaches that the PDE inhibitor is a compound which can inhibit the enzymatic activity of one or more of the subtypes of the enzyme phosphodiesterase (PDE), therefore preventing the inactivation of the intracellular second messengers cAMP or cGMP [0092]. PDE inhibitors may be employed in combination with a neuraminidase to treat an influenza viral infection [0093]. Exemplary PDE inhibitors for use in the invention are shown in Table 1, which includes the PDE3 inhibitor, Enoximone (4-methyl-5-{[4-(methylsulfanyl)phenyl]carbonyl}-2,3-dihydro- 1H-imidazol-2-one) and numerous other compounds that inhibit PDE3 (page 10).
Claim 16-18 of Altmeyer et al. claim a method for treating or preventing a viral infection caused by an influenza virus in a patient, said method comprising administering to said patient a first compound that is a neuraminidase inhibitor and a second compound that is a PDE inhibitor in amounts that together are sufficient to treat or prevent said viral infection in said patient, wherein said PDE inhibitor is a compound in Table 1 or an analog thereof, which includes the PDE3 inhibitor, Enoximone.
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to select enoximone as a PDE3 inhibitor for treating a virus according to the teachings of Altmeyer et al. since Altmeyer et al. specifically teaches that enoximone is a suitable PDE3 inhibitor suitable for the methods disclosed therein. Thus an ordinary skilled artisan would have been motivated to select enoximone with a reasonable expectation of similar success. Thus, although Altmeyer includes enoximone on a list that includes other PDE inhibitors, a prima facie case of obviousness can still be established since picking one of a finite number of known solutions to a known problem is prima facie obvious. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007).
Thus claim 2 is rendered obvious in view of the cited prior art teachings.
Claims 1, 2 and 5-11 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. WO 2018/026812 A1.
Claims 1, 2 and 5-11 of the instant application claims a method of treatment of a viral infection, such as a respiratory viral infection such as an infection by human respiratory syncytial virus (RSV), the method comprising administering a PDE3-inhibitor or a pharmaceutically acceptable salt thereof such as enoximone to a subject in need thereof.
Chen et al. teaches methods, pharmaceutical compositions, and kits directed to antiviral therapy, wherein the antiviral activity of the compounds is tolerant of a wide diversity of viral serotypes and species, being effective against Zika virus; Japanese encephalitis virus; dengue virus strains: DENV1 Hawaii, DENV2 PL046, DENV3 H087, and DENV4 H241; and influenza H1N1 (abstract). Chen et al. further teaches in some embodiments, the virus may be one of: Adenovirus; Lassa virus; hepatitis B virus; cytomegalovirus, Influenza A; measles virus; mumps virus; respiratory syncytial virus; coxsackie virus; hepatitis A virus; Chikungunya; and rubella virus [0055].
Chen et al. teaches in several embodiments, the method may include co-administering a phosphodiesterase inhibitor to the subject, wherein the phosphodiesterase inhibitor may include, for example, one or more of a phosphodiesterase 3 inhibitor and a phosphodiesterase 5 inhibitor ([0058] and [0099] [00102]). Chen et al. teaches that the phosphodiesterase 3 inhibitor may include, for example, one or more of: inamrinone, cilostazol, milrinone, enoximone, anagrelide, pimobendane, theophylline, meribendan, trequinsin, 4,5- dihydro-6-(4-(imidazol-l -yl)phenyl)-5-methyl-3(2H)-pyridazinone, N-{2-[(2E)-2- (mesitylindno)-9, 10-dimethoxy-4-oxo-6,7-dihydro-2H-pyrinddo[6, l-a]-isoquinolin-3(4H)- yl] ethyl} urea, and the like [0058].
Chen et al. specifically teaches the treatment of one of the following viruses: Ebola, Marburg, Lassa fever, hepatitis A, hepatitis B, serotype 5 adenovirus, coxsackie virus B4, Chikungunya, mumps, measles, rubella, respiratory syncytial virus a, respiratory syncytial virus b, cytomegalovirus, influenza A, and influenza B ([0077] and [0079]).
Claims 1, 10, 19 and 49 specifically claim a method of treating a virus, the virus being one of: Adenovirus; Lassa virus; hepatitis B virus; cytomegalovirus, Influenza A; measles virus; mumps virus; respiratory syncytial virus; coxsackie virus; hepatitis A virus; Chikungunya; and rubella virus, further comprising co-administering a phosphodiesterase inhibitor to the subject.
Chen et al. does not specifically teach administering enoximone for treating RSV.
Although Chen et al. does not specifically teach administering enoximone for treating RSV, as detailed above, Chen et al. teaches treating a virus which may be selected as respiratory syncytial virus and also teaches that the virus may be treated further comprising administering a PDE3 inhibitor such as enoximone.
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to treat any virus disclosed in Chen et al. including RSV with a reasonable expectation of similar success. Furthermore, an ordinary skilled artisan would have been specifically motivated to combine a PDE3 inhibitor such as enoximone for the treatment of the viral infection with a reasonable expectation of improved results. Thus although Chen et al. includes RSV and enoximone on lists that include other viruses and PDE inhibitors, respectively a prima facie case of obviousness can still be established since picking one of a finite number of known solutions to a known problem is prima facie obvious. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007).
Thus the cited claims of the instant application are rendered since Chen et al. specifically teaches and claims a method of treatment of a viral infection, wherein the viral infection may be selected as RSV, the method comprising administering a PDE3-inhibitor which may be selected as enoximone to a subject in need thereof. Moreover, since Chen et al. renders obvious the administration of a PDE3 inhibitor as claimed for the treatment of a viral infection, the method of Chen et al. will necessarily treat the same symptoms of the viral infection as claimed. Thus claims 7 and 8 of the instant application are rendered obvious.
In addition, since Chen et al. renders obvious the administration of a PDE3 inhibitor as claimed for the treatment of a viral infection, the same effects as claimed in claim 9 will necessarily be achieved. Claim 10 is rejected since Chen et al. does not teach or suggest that the PDE-3 inhibitor is for achieving bronchodilation or for treating an allergic reaction.
Thus the cited claims of the instant application are rendered obvious in view of the cited prior art teachings.
Conclusion
Claims 1, 2 and 5-11 are rejected. Claims 3, 4, and 12-15 are withdrawn. No claims are allowed.
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/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
KRM