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 371 of PCT/US2021/029608 (04/28/2021) which has PRO 63/017,199 (04/29/2020).
Request for Continued Examination (RCE)
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 1/16/26 has been entered.
Status
Rejections and objections not reiterated are withdrawn.
Claims 31-40 and 42 are pending.
New Claim Rejections - 35 USC § 103
Claims 31-40, 42 are rejected under 35 U.S.C. 103 as being unpatentable over Villar et al. (Crit Care Expl 2020 (14 April 2020); 2:e0111, 5 pages) in view of Long et al. (Int J Clin Exp Med 2016;9(5):8865-8873).
Villar teaches treating COVID-19-associated ARDS by administering dexamethasone IV 20mg/day (p. 3). Villar teaches the vital importance of treating inflammation in COVID-19 patients (p. 3: “What ‘kills’ COVID-19 patients is dysregulated systemic inflammation”). Villar cites to Long as teaching the study of corticosteroid therapy (CST) dose effects in SARS and supporting the treatment of COVID-19 with CST (p. 3: “positive findings of two large studies (5,327 patients with severe acute respiratory syndrome [SARS] [24] and 2,141 patients with influenza H1N1 pneumonia [25]) that evaluated the impact of time, dose, and duration of CST and reported a significant reduction in mortality with dosage”; Ref 24 is Long).
Long teaches “GC [(glucocorticoid)] therapy was beneficial for severe SARS patients” (Abstract) using data from large studies with the standard dexamethasone equivalent measure of GC (p. 8866: “To evaluate the effect of GC accurately in terms of the dose-response relationship, GC transformation was performed as: 4 mg methylprednisolone (MP) =0.75 mg dexamethasone =20 mg hydrocortisone. MP dosage was adopted as standard GC dosage in following analysis, i.e. 1 mg GC equals to 1 mg MP.”). Long concluded that high dose GC, >160 mg/d GC, therapy was successful to prolong survival time of patients with ARDS (p. 8870: “This study demonstrated that the usage of GC in treating ALI and ARDS prolonged the survival time of the patients significantly (P=0.03) and decreased the risk of death by 80%. … In severe cases, -160 mg/d and >160 mg/d at the beginning, -160 mg/d and >160 mg/d in the first three days, -80 mg/d and -160 mg/d average daily doses, -160 mg and >160 mg daily maximum doses, and -3000 mg, -6000 mg, and >6000 mg accumulated GC doses were shown beneficial to patients”; p. 8871: “high dose GC, which should be used as double of first dose or pulse therapy, should be prescribed to severe patients at early stage of infection to control clinical progress and alleviate symptoms”). Long teaches “[t]he dose-response relationship showed the bigger accumulated dose, the better effects in severe cases” (p. 8871). Long teaches use of the maximum dose if a patient’s condition is not controlled (p. 8871: “It was suggested that clinicians might try higher GC doses in first three days and maximum dose if MERS patients’ condition cannot be controlled well with GC dose above mentioned”). Using Long’s standard conversion, 1 mg MP = 0.75/4 mg dexamethasone; thus, 160 mg/day MP is equivalent to 30 mg/day dexamethasone; 6000 mg MP is equivalent to a total dose of 1125 mg dexamethasone.
Claim 31 has the language “administering a glucocorticoid to the patient at a dose equivalent to at least 6 mg/kg human equivalent dose (HED)” but does not specify the time course of administration. According to the instant specification at [0086] the dose can be given over 72 hours as a “total dose” in contrast to “a single acute dose”. Thus, the dose claim language under a BRI is interpreted as encompassing both “total dose” and “a single acute dose”.
Regarding claim 31, Villar teaches administration of corticosteroids of dexamethasone at 20 mg and methylprednisone at 1 mg/kg (p. 3, Fig. 3) and recognized that dose was a results effective variable (p. 3: “evaluated the impact of time, dose, and duration of CST and reported a significant reduction in mortality with dosage”) but does not teach administration at 6 mg/kg.
One of ordinary skill in the art of pharmacy and therapeutics following the teaching of Villar formulating a dose for a COVID-19 patient would have considered the teaching of Long, as cited by Villar. As taught by Long, one of ordinary skill in the art would have considered trying a high dose of dexamethasone, including > 160 mg/day. One of ordinary skill in the art would have considered obvious to try increasing the dose of an established results-effective variable, as is specifically taught by Villar, and Long. Thus, one of ordinary skill in the art would have considered increasing the dexamethasone dose to > 160 mg/day to over 1125 mg total dose until a desirable response was achieved and arrive at the claimed invention with a reasonable expectation of success.
Regarding claims 32-39, as with claim 31 the prior art teaches administration in the same manner as in the instant disclosure and thus would necessarily have the same effect as in the instant claims.
Regarding claim 40, although Villar teaches treating COVID-19-associated ARDS by administering dexamethasone IV 20mg/day (p. 3), Villar does not teach a dose of at least 12 mg/kg. As with claim 31, One of ordinary skill in the art of pharmacy following the teaching of Villar formulating a dose for a COVID-19 patient would have considered the teaching of Long, as cited by Villar. As taught by Long, one of ordinary skill in the art would have considered trying a high dose of dexamethasone, including > 160 mg/day. One of ordinary skill in the art would have considered obvious to try increasing the dose of an established results-effective variable, as is specifically taught by Villar, and Long. Thus, one of ordinary skill in the art would have considered increasing the dexamethasone dose to > 160 mg/day to over 1125 mg total dose until a desirable response was achieved and arrive at the claimed invention with a reasonable expectation of success.
Regarding claims 42, Villar teaches administration of dexamethasone.
With each of the claims, the level of skill in the art is very high such that one of ordinary skill in the art would consider routine the combination of elements from the teaching of the art. One of ordinary skill in the art would have recognized that the results of the combination would be predictable due to the well-known nature and optimizations routinely performed in the art. Thus, one of ordinary skill in the art would have arrived at the invention as claimed before the effective filing date with a reasonable expectation of success.
Response to Remarks - 35 USC § 103
Applicant argues that there is nothing in Villar that suggests increasing the amount of glucocorticoid. This argument is not persuasive because one of ordinary skill in the art would have considered the teaching of Villar in view of Long and considered Long’s teaching of increasing the dose in severe patients to > 160 mg/day and to over 1125 mg total dose until a desirable response was achieved in the established result-effective variable and arrive at the claimed invention with a reasonable expectation of success.
Applicant argues that the Examiner “fail[ed] to consider the claimed invention as a whole, in contravention of the requirements under 35 U.S.C. § 103”. This argument is not persuasive because the claimed invention was fully considered, including as a whole, consistent with 35 USC 103 and the MPEP. The prior art teaches the same method of therapy applied to the same subject differing only by the specific dose which was suggested to increase by the prior art.
New Double Patenting Rejections
Claims 31-40, 42 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 43 of copending Application No. 17801293 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application claim is to a method of treating an infectious disease, which one of skill in the art would find as including COVID-19 (‘193 specification at [0052]) when construing the claim term, by administering a glucocorticoid which anticipates or renders obvious the instant claims in view of Villar et al. (Crit Care Expl 2020 (14 April 2020); 2:e0111, 5 pages) in view of Long et al. (Int J Clin Exp Med 2016;9(5):8865-8873) as detailed in the 35 USC 103 rejection above and incorporated herein.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Remarks - Double Patenting
Applicant requested the rejection be held in abeyance. Thus, the rejection is maintained.
Conclusion
No claims allowed.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626