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 .
Change of Examiner
This application has been reassigned to Examiner Valenrod whose contact information is provided at the conclusion portion.
Withdrawn rejections
Rejection of claims 1-7 and 9-22 are under 35 USC 112(a) is withdrawn in view of arguments presented on 8/6/26.
Maintained rejections
Rejections under 35 USC 103 are maintained. New claim 23 is within the scope of rejected claim 1 and is of the same scope as rejected claim 8. Claim 23 is added to the rejection of record. Applicant’s arguments are addressed following repeated text of rejections of record.
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.
Claims 1-10, 13-14, and 19-22 are rejected under 35 U.S.C. 103 as being unpatentable over Hong et al. (US 2023/0000771 A1, published 01/05/2023, with an effectively filed date of 06/17/2021).
Hong teaches a method of treating a pulmonary disease, comprising administering by oral inhalation a therapeutically effective amount of a self-assembled therapeutic dendron-micelle comprising an encapsulated BRD4 ligand (claim 18 teaches oral inhalation and depends from claim 1, which teaches the BRD4 ligand). Hong further teaches treating a subject suffering from SARS-CoV-2 comprising administering an encapsulated BRD4 ligand (claim 20). Hong teaches that exemplary delivery by oral inhalation includes a nebulizer device (p. 11, para 0094).
Hong teaches the BRD4 ligand can be ID-1, depicted below (claim 15).
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Compound ID-1 is a compound of instant Formula I wherein R1 is OH and R2 is 4-methyl-piperazine.
More broadly, Hong teaches the BRD4 ligand can be of Formula (ID), depicted below (claim 12, p. 22, right col.).
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When R14 is C-3 alkyl substituted only with 4 methyl piperazine (rather than with both OH and 4 methyl piperazine as in Compound ID-1), the compound depicted below is reached.
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This is a compound of instant Formula I wherein R1 is hydrogen and R2 is 4 methyl piperazine, as recited in instant claim 2.
Hong does not explicitly teach a method of treating a coronavirus in a subject comprising administering Compound ID-1. Hong also does not explicitly teach a compound of instant Formula I wherein R1 is H. Hong also does not teach the administration of Compound ID-1 with another therapeutic agent.
Regarding claims 1 and 7-9, although Hong does not explicitly teach a method of treating SARS-CoV-2 comprising administering Compound ID-1, it would have been prima facie obvious to one of ordinary skill in the art prior to the filing of the instant application to do so. One would have been motivated and had a reasonable expectation of success given Hong teaches a self-assembled therapeutic dendron-micelle comprising an encapsulated BRD4 ligand can be administered to treat SARS-CoV-2 infection and given Hong explicitly recites Compound ID-1 as a BRD4 inhibitor for use in the dendron-micelle.
Regarding claims 2-6, a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (discussed in more detail below) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990) (discussed below and in MPEP § 2144) for an extensive review of the case law pertaining to obviousness based on close structural similarity of chemical compounds. See also MPEP § 2144.08, subsection II.A.4.(c).
Thus, it would have been obvious to synthesize and administer the following compound of instant Formula (I):
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One would have been motivated and had a reasonable expectation of success to do so given that Hong teaches compounds of Formula ID are useful in treating SARS-CoV-2 infection and that Compound ID-1, which is structurally similar to the compound of instant claim 7 and differing only in the presence of an -OH group, is particularly useful as a BRD4 ligand.
Regarding claim 10, it would have been obvious to administer Compound ID-1 to a patient via oral inhalation to treat SARS-CoV-2 since Hong teaches a method of treating SARS-CoV-2 comprising administering Compound ID-1 via oral inhalation.
Regarding claim 11, it would have been obvious to administer Compound ID-1 to a patient via oral inhalation to treat SARS-CoV-2 since Hong teaches exemplary delivery by oral inhalation includes a nebulizer device.
Regarding claim 13, the courts have recognized that combining equivalents known for the same purpose supports a prima facie case of obviousness. See MPEP 2144.06: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious); and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine).
Because Hong teaches administering Compound ID-1 to treat SARS-CoV-2 in a patient, it would have been obvious to one of ordinary skill in the art prior to the filing of the instant application to administer Compound ID-1 in combination with one or more therapeutic agents or treatments to treat SARS-CoV-2 in a patient. One would have had a reasonable expectation of success to do so based on the teaching of Hong because each agent works independently to treat SARS-CoV-2 and thus there is an expectation that the combination would work as well.
Regarding claim 14, because Compound ID-1 is known to treat SARS-CoV-2 in a patient, it would have been obvious to one of ordinary skill in the art prior to the filing of the instant application to administer Compound ID-1 in combination with standard of care co-treatment to treat SARS-CoV-2 in a patient. One would have had a reasonable expectation of success in doing so based on the teaching of Hong because each agent works independently to treat SARS-CoV-2 and thus there is an expectation that the combination would work as well.
Regarding claims 19-22, it would have been obvious to administer Compound ID-1 to treat mild to moderate COVID-19 (as recited in claim 19), severe COVID-19 (as recited in claim 20), a patient at high risk for progressing to severe COVID 19 (as recited in claim 21), and a patient suffering from hypertension or diabetes (as recited in claim 22). One would have been motivated and had a reasonable expectation of success to do so given that Hong teaches Compound ID-1 is useful for treating COVID-19.
Claims 1, 11, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Hong et al. (US 2023/0000771 A1) in view of Brasier et al. (US 11,389,433 B2).
As discussed above in this Office action, Hong teaches a method of treating SARS-CoV-2 in a patient, comprising administering Compound ID-1. Hong does not teach a dosage or treatment regimen.
Brasier teaches ZL0516 (cols 13-14, Table 1). This is the same as Compound ID-1 as taught by Hong, referenced above.
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Brasier teaches administering ZL0516 to a subject to treat one or more clinical features of airway remodeling (claim 1 of Brasier) at a dosage of 0.1 to 100 mg/kg (claim 2 of Brasier). Brasier further teaches wherein the one or more clinical features is fibrosis. Brasier teaches a preferred dosage of between about 1 and 100 μg/kg body weight (col. 16, lines 63-66) and administration every 24 hours (col. 17, lines 3-4). Assuming a body weight of 70 kg, Brasier teaches a dosage of between about 0.07 to about 7 mg.
Regarding claim 11, it would have been obvious before the effective filing date of the instant application to administer Compound ID-1 once a day to treat a patient infected with a coronavirus. One would have been motivated and had a reasonable expectation of success given Hong teaches Compound ID-1 can be administered to treat SARS-CoV-2 infection in a patient and given Brasier teaches Compound ID-1 (ZL0516) can be safely and effectively administered every 24 hours.
Regarding claim 18, it would have been prima facie obvious to one of ordinary skill in the art to utilize the amount of Compound ID-1 and the treatment regimen taught by Brasier as a starting point for optimizing the amount and treatment regimen of Compound ID-1 utilized to treat SARS-CoV-2 as taught by Hong since Hong teaches Compound ID-1 is useful for treating SARS-CoV-2 and because dosage and treatment regimen are result-effective variables, i.e. a variable that achieves a recognized result. Therefore, the determination of the optimum or workable dosages would have been well within the practice of routine experimentation by the skilled artisan. Furthermore, absent any evidence demonstrating a patentable difference between the compositions and the criticality of the claimed dosage range, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II)(A) and In re Aller, 220 F. 2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). ("[W]here the general conditions of claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Claims 1 and 15-17 are rejected under 35 U.S.C. 103 as being unpatentable over Hong (US 2023/0000771 A1) as applied to claim 1 above, and further in view of Kim et al. (PLOS Medicine 17(12): e1003501).
Kim teaches the risk of progression to severe course and mortality was significantly reduced with corticosteroids and remdesivir compared to standard care for moderate to severe COVID-19 patients in non-ICU; corticosteroids were also shown to reduce mortality rate (p. 2, para. 1, lines 1-7). Kim also teaches that oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days reduces 28-day mortality (p. 22, para. 1, lines 8-10).
Regarding claim 15, as discussed above in this Office action (see rejection for claim 13), the courts have recognized that combining equivalents known for the same purpose supports a prima facie case of obviousness (see MPEP 2144.06). Therefore, because Compound ID-1 and corticosteroids are known individually to treat SARS-CoV-2 in a patient, it would have been obvious to one of ordinary skill in the art prior to the filing of the instant application to administer Compound ID-1 in combination with corticosteroids to treat SARS-CoV-2 in a patient. One would have been motivated to combine the teachings of Hong and Kim and had a reasonable expectation of success in doing so because each agent works independently to treat SARS-CoV-2 and thus there is an expectation that the combination would work as well.
Regarding claim 16, because Compound ID-1 and remdesivir are known individually to treat SARS-CoV-2 in a patient, it would have been obvious to one of ordinary skill in the art prior to the filing of the instant application to administer Compound ID-1 in combination with remdesivir to treat SARS-CoV-2 in a patient. One would have been motivated to combine the teachings of Hong and Kim and had a reasonable expectation of success in doing so because each agent works independently to treat SARS-CoV-2 and thus there is an expectation that the combination would work as well.
Regarding claim 17, because Compound ID-1 and dexamethasone are known individually to treat SARS-CoV-2, it would have been obvious to one of ordinary skill in the art prior to the filing of the instant application to administer Compound ID-1 in combination with dexamethasone to treat SARS-CoV-2 in a patient. One would have been motivated to combine the teachings of Hong and Kim and had a reasonable expectation of success in doing so because each agent works independently to treat SARS-CoV-2 and thus there is an expectation that the combination would work as well.
Reply to applicant’s remarks
Arguments presented on 8/6/26 have been fully considered and found to be not persuasive. Applicants argue that the claims are directed to use of free compound of formula I while Hong’s teaching is directed to administration dendron-micelle system which encapsulates compound I. This argument is not persuasive because applicant’s interpretation of the scope claims is not consistent with the pending claims. Applicants are relying on limitations not found in the claims.
Claim 1 reads: “A method of treating a patient infected with a coronavirus comprising administering a compound of Formula I…”. Applicants argue that the claims are directed to administration of a “free compound of formula I”, however the claims are not limited to “free compound of formula I”.
Specification in paragraph [00016] defines the term “comprising”:
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According to applicant’s definition, the term “comprising” does not exclude additional unrecited elements. The encapsulation of compound of formula I as taught by Hong constitutes an additional unrecited element and is therefore within the scope of current claims. Administration of encapsulated BRD4 ligand to subjects with SARS-CoV-2 infection as suggested by Hong reads on the pending claims.
Conclusion
Claims 1-23 are pending
Claims 1-23 are rejected
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to YEVGENY VALENROD whose telephone number is (571)272-9049. The examiner can normally be reached Mon-Fri 9am-5pm.
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/YEVGENY VALENROD/Primary Examiner, Art Unit 1628
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