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 .
Status of the Claims
Claims 1 – 31 are pending and rejected.
Election/Restriction
Applicant’s election without traverse of rhinovirus as the respiratory enterovirus infection, and COPD (chronic obstructive pulmonary diseases) as the underlying condition in the subject in the reply filed on August 6, 2026 is acknowledged.
Examination: Applicant’s elected species are not allowable. Subject matter not embraced by the elected embodiment or the scope searched is therefore withdrawn from further consideration.
Priority
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Information Disclosure Statement
The information disclosure statement (IDS) submitted on August 8, 2024 and December 23, 2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement are being considered by the examiner.
Claim Objections
Claim 3 is objected to because of the following informalities:
The limitation “… respiratory enterovirus is selected from a rhinovirus, echovirus, EV-68, EV-71, coxsackie virus, a non-polio enterovirus, and combinations thereof” is grammatically incorrect because it does not recite proper language for the group of alternatives. In order to overcome the objection, Applicant may amend the limitation as follows: “… respiratory enterovirus is selected from a rhinovirus, EV-68, EV-71, coxsackie virus, and a non-polio enterovirus, or any.
Appropriate correction is required.
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.
Claim 10 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
The claim recites several limitations containing exemplary language (emphasis added):
fibrosis such as tuberculosis (TB), idiopathic pulmonary fibrosis (IPF), other major respiratory diagnosis (e.g., pneumonia, aspergillosis) (see, lines 3-5 of the claim), and
nasal disease (e.g., nasal polyposis, significant septal deviation, chronic rhinosinusitis, etc.)
The phrases “e.g.” (interpreted as “for example”), “such as” and “etc.” (interpreted as “or the like”) renders the claim indefinite because it is unclear whether the limitations following the phrases are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 102
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.
(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 1 – 3, 6 and 10 – 27 are rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Lambert et al. WO2011/127538 A1, cited in IDS dated August 8, 2024.
With respect to claims 1 – 3, 10 – 11, Lambert et al. teach “method for treating or alleviating symptoms of COPD comprising administering 3-ethoxy-6-{2-[1-(6-methyl-pyrid~zin-3-yl)-piperidin-4-yl]-ethoxy}-benzo[d]isoxazole (vapendavir in the instant claims) or a pharmaceutically acceptable salt thereof to a subject in need thereof”. See, e.g., page 5, lines 23-26. The subject “COPD sufferer” (which includes one of the four GOLD stages in claim 11) has a HRV (Human Rhinovirus) or is at risk of HRV infection. See, e.g., page 6, lines 17-18. Lambert further teaches a Phase-II double-blind, placebo-controlled study of orally administering said compound to determine the prophylactic efficacy, safety and pharmacokinetics in an experimental rhinovirus challenge model. The compound was administered for 10 days dosing with either 25 mg, 100 mg or 400 mg b.i.d. The study concluded “when used prophylactically, 3-Ethoxy-6-{2-[1-(6-methyl-pyridazin-3-yl)-piperidin-4-yl)-ethoxy}-benzo[d]isoxazole reduced the incidence of HRV39 infection in subjects in a dose-related manner… [t]here was a dose-related difference to placebo in HRV viral load (AUCculture and AUCPCR) and in peak viral load between Days 1 to 6… [t]hese differences were statistically significant compared to placebo at the 400mg bid dose level”. See, e.g., page 16, lines 7-12.
With respect to claim 6, please note the limitation “the therapeutically effective amount of vapendavir or a pharmaceutically acceptable salt thereof is an amount that achieves a Cmax of about 2000 to about 12000 ng/ml” is an intended use limitation as governed by MPEP §2111.02(II). Intended use limitations are interpreted based on the structural limitations they impart to the invention. In this case, the intended use only requires a therapeutically effective amount of vapendavir in an amount that achieves within said Cmax range. The intended use does not impart any specific limitations to the structure or the method of administration. Based on the teachings of Lambert et al. administering the therapeutically effective amount of vapendavir is capable of achieving a Cmax of about 2000 to about 12000 ng/ml.
With respect to claim 12, Lambert et al. also teach a Phase II Multicentre, Randomised, Double-Blind, Placebo-controlled, parallel-arm study of two dose levels of vapendavir in asthmatic adults with symptomatic Human Rhinovirus infection. Lambert teaches that patients “continue to maintain asthma medications according to their usual instructions and medication details such as dose and time of all dosing occasions” during the administration of the study. See, page 20, lines 1-3.
With respect to claim 13, Lambert teaches administration at the 400 mg bid dose level resulted in statistically significant difference in HRV viral load (AUCculture and AUCPCR) and in peak viral load between Days 1 to 6. See, e.g., page 16, lines 7-12, and Figure 1.
With respect to claims 14 – 27, Lambert defines the “symptoms” of asthma or COPD as “reduced lung function (including reduced lung volume), coughing, wheezing, breathlessness and airway necrosis”. See, e.g., page 14, lines 27-29. Further, “alleviating” refers to the “reduction of the severity or frequency of the symptom or both”. See, e.g., page 15, lines 1-2. According to Example 1, Lambert teach that the incidences of infection between the placebo and each dose level of the compound are measured and compared using Fisher’s Exact Test. See, e.g., page 16, lines 4-5. Further, according to Example 3, the primary end point and rationale in the study is calculated on the mean difference in the Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) severity score. See, e.g., page 19, line 25 – page 20, line 1. The secondary endpoints can be selected from any one or more of the following criteria:
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See, e.g., page 20, lines 6-12. Therefore, Lambert et al. teach that each of the claimed decrease or preventing an increase in the subject’s E-RS, peak LRSS, peak URSS, Exact-Pro, Exact-RS, lung function, FEY-1, FVC, FEV1/FVC ratio, PEF, peak nasal lavage viral load, peak sputum lavage viral load, AUC nasal viral load, and AUC sputum viral load in the subject can be compared prior and after the treatment.
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 – 27 are rejected under 35 U.S.C. 103 as being unpatentable over Lambert et al. WO2011/127538 A1 in view of Gross et al. US2016/0287564 A1, cited in IDS dated August 8, 2024.
Determining the scope and contents of the prior art
Lambert et al. teach “method for treating or alleviating symptoms of COPD comprising administering 3-ethoxy-6-{2-[1-(6-methyl-pyrid~zin-3-yl)-piperidin-4-yl]-ethoxy}-benzo[d]isoxazole (vapendavir in the instant claims) or a pharmaceutically acceptable salt thereof to a subject in need thereof”. See, e.g., page 5, lines 23-26. The subject “COPD sufferer” (which includes one of the four GOLD stages in claim 11) has a HRV (Human Rhinovirus) or is at risk of HRV infection. See, e.g., page 6, lines 17-18. Lambert further teaches a Phase-II double-blind, placebo-controlled study of orally administering said compound to determine the prophylactic efficacy, safety and pharmacokinetics in an experimental rhinovirus challenge model. The compound was administered for 10 days dosing with either 25 mg, 100 mg or 400 mg b.i.d. The study concluded “when used prophylactically, 3-Ethoxy-6-{2-[1-(6-methyl-pyridazin-3-yl)-piperidin-4-yl)-ethoxy}-benzo[d]isoxazole reduced the incidence of HRV39 infection in subjects in a dose-related manner… [t]here was a dose-related difference to placebo in HRV viral load (AUCculture and AUCPCR) and in peak viral load between Days 1 to 6… [t]hese differences were statistically significant compared to placebo at the 400mg bid dose level”. See, e.g., page 16, lines 7-12.
Ascertaining the differences between the prior art and the claims at issue
Compared to claims 4 – 5 and 8 – 9, Lambert et al. does not explicitly teach the method, wherein the therapeutically effective amount of vapendavir is a single loading dose of about 1,000 mg followed by a maintenance dose of 500 mg every 12 hours for about 4 to 10 days (claim 4), or a total of about 13 maintenance doses (claim 5), and administering the single loading dose and maintenance doses within about 30 minutes of the subject consuming a meal with solid food (claims 8 – 9).
Rationale for a prima face case of obviousness
According to MPEP §2141(III), two of the rationales in the KSR decision states “(E)
“Obvious to try” – choosing from a finite number of identified, predictable solutions, with a
reasonable expectation of success… (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention”. KSR, 550 U.S. at 418, 82 USPQ2d at 1396. Gross et al. teach a method of treating disease, including viral infections, comprising orally administering compounds of general formulae I – VI, wherein the compound is administered with a meal or in fed mode. See, e.g., paragraph [0005]. Gross specifically teaches that the compounds can be administered between 100 mg to 10 g, preferably 1200 mg, per day. See, e.g., paragraph [0314]-[0317]. While Lambert does not specifically teach administering a single loading dose of about 1,000 mg of vapendavir, it does teach that the compound can be administered in a single or multidose form. See, e.g., page 13, line 2. Further, patients in the Phase II Multicentre, Randomised, Double-Blind, Placebo-controled, parallel-arm study were administered with a total dosage of 800 mg (400 mg BID) with further clinic visits out to 28 days. MPEP §2144.05(II)(A) states:
“Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)”.
Thus, a person having ordinary skill in the art would have been motivated to perform routine experimentation, such as optimization of the dose concentration and working protocol of vapendavir in the administration. The purpose of the routine experimentation would have been to determine which concentration of vapendavir would be optimal to provide the best pharmaceutical properties and successfully treat rhinovirus in the human subject having COPD.
With respect to claim 7, Gross teaches the method of treating disease, including viral infections, comprising orally administering compounds of general formulae I – VI, wherein the compound is administered with a meal or in fed mode. See, e.g., paragraph [0005].
Claims 1 – 3, 6 and 10 – 31 are rejected under 35 U.S.C. 103 as being unpatentable over Lambert et al. WO2011/127538 A1 in view of Av-Gay et al. US2017/0239289 A1, cited in IDS dated August 8, 2024.
Determining the scope and contents of the prior art
Lambert et al. teach “method for treating or alleviating symptoms of COPD comprising administering 3-ethoxy-6-{2-[1-(6-methyl-pyrid~zin-3-yl)-piperidin-4-yl]-ethoxy}-benzo[d]isoxazole (vapendavir in the instant claims) or a pharmaceutically acceptable salt thereof to a subject in need thereof”. See, e.g., page 5, lines 23-26. The subject “COPD sufferer” (which includes one of the four GOLD stages in claim 11) has a HRV (Human Rhinovirus) or is at risk of HRV infection. See, e.g., page 6, lines 17-18. Lambert further teaches a Phase-II double-blind, placebo-controlled study of orally administering said compound to determine the prophylactic efficacy, safety and pharmacokinetics in an experimental rhinovirus challenge model. The compound was administered for 10 days dosing with either 25 mg, 100 mg or 400 mg b.i.d. The study concluded “when used prophylactically, 3-Ethoxy-6-{2-[1-(6-methyl-pyridazin-3-yl)-piperidin-4-yl)-ethoxy}-benzo[d]isoxazole reduced the incidence of HRV39 infection in subjects in a dose-related manner… [t]here was a dose-related difference to placebo in HRV viral load (AUCculture and AUCPCR) and in peak viral load between Days 1 to 6… [t]hese differences were statistically significant compared to placebo at the 400mg bid dose level”. See, e.g., page 16, lines 7-12.
Ascertaining the differences between the prior art and the claims at issue
Compared to claims 28 – 31, Lambert et al. does not explicitly teach reducing the duration of viral shedding (claim 28), reducing or preventing an increase in the subject’s peak sputum bacterial load compared to the subject’s peak sputum lavage bacterial load prior to treatment (claim 29), reducing or preventing an increase in the subject’s AUC sputum bacterial load compared to the subject’s AUC sputum lavage bacterial load prior to treatment (claim 30) and reducing the number of days wherein the subject is positive for bacteria in the sputum (claim 31).
Rationale for a prima face case of obviousness
According to MPEP §2141(III), one of the rationales in the KSR decision states “(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention”. KSR, 550 U.S. at 418, 82 USPQ2d at 1396. Av-Gay et al. teach a method for treating diseases such as inflammation, bronchiolitis and cystic fibrosis in a human subject in need thereof, comprising repeated administrations “for a time sufficient to: (a) reduce the level of at least one inflammatory biomarker in the human subject when compared to the level of the inflammatory biomarker prior to the administration; and (b) reduce the microbial (bacterial) density by 1 to 2 log units as measured by colony forming units in the human subject when compared to the microbial density prior to the administration”. See, e.g., Abstract. Specifically, Av-Gay teaches reducing the duration of eliminating methicillin-sensitive Staphylococcus aureus (MSSA) in the treatment in “Patient 3” (CFSCH03). See, e.g., paragraph [0492], and Figure 2B. A person having ordinary skill in the art would have been motivated to perform routine experimentation, such as reducing the time of the infection. The purpose of the routine experimentation would have been to determine which concentration of vapendavir would be optimal to reduce the duration of viral shedding (claim 28), reduce an increase in the subject’s peak sputum bacterial load compared to the subject’s peak sputum lavage bacterial load prior to treatment (claim 29), reduce an increase in the subject’s AUC sputum bacterial load compared to the subject’s AUC sputum lavage bacterial load prior to treatment (claim 30) and reduce the number of days wherein the subject is positive for bacteria in the sputum (claim 31).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1 – 31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 30 of copending Application No. 18/604,259 (U.S. Publication 2024/0307389 A1), cited in IDS dated December 23, 2024. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claim 1 in US ‘259 is directed to a method:
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Dependent claims 2 – 30 in US ‘259 are directed to similar, if not the same, scope or subject matter as claimed in the instant claims 2 – 31. Thus, the claims in US ‘259 render the instant claims unpatentable for anticipatory-type double patenting.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 – 31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7 – 62 of copending Application No. 19/304,285 (U.S. Publication 2026/0048050 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claim 7 in US ‘259 is directed to a method:
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Dependent claims 8 – 62 in US ‘285 are directed to similar scope or subject matter as claimed in the instant claims 2 – 31. Thus, the claims in US ‘285 render the instant claims unpatentable for anticipatory-type double patenting.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sagar Patel whose telephone number is (571)272-1317. The examiner can normally be reached Monday - Friday: 9am to 5pm EST.
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/Sagar Patel/Examiner, Art Unit 1626
/KAMAL A SAEED/Primary Examiner, Art Unit 1626
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