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 .
Application Status
The amendment filed on 11/21/2025 is acknowledged and has been entered.
Claims 1-12 and 17-22 are currently pending and under consideration.
Information Disclosure Statement
The information disclosure statement filed on 11/21/2025 is acknowledged and has been considered except where lined through.
Rejections Withdrawn in view of Applicants amendments:
The rejection of Claim(s) 13-16 under 35 U.S.C. 102(a)(1) as being anticipated by Nickoloff-Bybel et al. (Brain, Behavior, and Immunity 82 (2019) 239-252) is withdrawn in view of Applicants cancellation of claims 13-16.
Rejections Withdrawn in view of Applicants arguments:
The rejection of Claim(s) 1-16 under 35 U.S.C. 103 as being unpatentable over Glazner, Gordon (US2002/0107193, 2002-08-08) referred to herein as “Glazner” in view of Cornelius et al. (Biochemical and Biophysical Research Communications (1989) 162(2), 852-856) and Ryanodex ® Label(revised on 7/2014) referred to herein as “Ryanodex” is withdrawn in view of Applicants arguments.
Rejections Maintained, but amended in view of Applicants Amendments
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 €n 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€ 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 1-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 17/995,604(‘604 reference application) or claims 1-20 of copending Application No. 17/995,602(‘602 reference application) claims 1-20 of copending Application No. 17/995,606(‘606 reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because
The ‘604 reference application claims a method of treating Severe Acute Respiratory Syndrome, inhibiting replication of SARS-CoV in a subject comprising administering to the subject dantrolene or a sodium salt thereof.
The ‘602 reference application claims a method of treating Covid 19, inhibiting replication of SARS-CoV in a subject comprising administering to the subject dantrolene or a sodium salt thereof.
The ‘606 reference application claims a method of treating coronavirus, inhibiting replication of coronavirus in a subject comprising administering to the subject dantrolene or a sodium salt thereof.
As such, the reference applications claim a species of the genus instantly claimed.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicants request that the above rejections be held in abeyance until allowable subject matter has been identified.
New rejections upon further consideration
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 –
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.
Claim(s) 9-12 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nickoloff-Bybel et al. (Brain, Behavior, and Immunity 82 (2019) 239-252).
Nickoloff-Bybel et al. teach that dopamine increases HIV entry into macrophages by increasing calcium release via an alternative signaling pathway (Title). Moreover, the publication teaches an HIV entry assay, wherein the calcium inhibitor dantrolene was added 60 minutes prior to inoculation and maintained in culture through the end of the inoculation period (page 241, 2nd column, 3rd full paragraph). Specifically, the publication teaches that post-hoc analysis showed that dopamine significantly increased HIV entry, and that treatment with dantrolene, alone or in the presence of dopamine, significantly reduced entry relative to the effect of dopamine alone (page 234, 2nd column, 2nd full paragraph). With regards to the dantrolene, the publication teaches that dantrolene sodium salt was used (page 241, 2.1 Reagents).
Since claims 9-12 do not specifically require that the host cell is within a subject, the claims have been interpret as being an in vitro system.
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.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claim(s) 1-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Glazner, Gordon (US2002/0107193, 2002-08-08) referred to herein as “Glazner” in view of Cornelius et al. (Biochemical and Biophysical Research Communications (1989) 162(2), 852-856), Ryanodex ® Label(revised on 7/2014) referred to herein as “Ryanodex” and Jacob et al. (Neuroscience Letters 2014; 575: 7-2).
Glazner teaches a method of treating HIV infection comprising administering an effective amount of a pharmaceutical composition comprising an IP3 receptor-mediated calcium channel modulator to an individual in need of said treatment (claim 6 of Glazner). Moreover, the publication teaches a method of treating a disorder such as a viral disease characterized by endoplasmic reticulum-dependent calcium release comprising administering an effective amount of a pharmaceutical composition comprising an IP3 receptor mediated calcium channel blocker (claims 14 and 19 of Glazner).
Glazner does not specifically teach that the IP3 receptor-mediated calcium channel modulator is dantrolene.
Cornelius et al. teach that inositol 1,4,5-trisphophate (IP3) is known to release calcium ions from intracellular stores thought to be part of the endoplasmic reticulum in animal cells, wherein the release is inhibited effectively by dantrolene (abstract). Specifically, Cornelius et al. teach that dantrolene is known to inhibit calcium release from animal cell sarcoplasmic reticulum after stimulation by IP3 (page 855, lines 7-8).
Ryanodex teaches that Ryanodex is the brand name for dantrolene sodium with initial FDA approval in 1974 for treatment of malignant hypothermia.
Jacob et al. teach that mitochondrial CA2+ accumulation is mainly mediated by the mitochondrial Ca2+ accumulation is mainly mediated by the mictochondrial Ca2+ uniporter (MCY), but recent reports also indicate that mitochondrial Ca2+ influx mechanisms are regulated not only by MCU, but also by multiple channels/transporters (Abstract). Specifically, Jacob et al. teach that dantrolene inhibits mitochondrial Ca2+ uptake induced by IP3-mediated Ca2+ release from the endoplasmic reticulum (ER)(page 9, Figure 1).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute IP3 receptor-mediated calcium channel modulator taught in the method of Glazner with dantrolene in view of the teachings of Cornelius et al., Ryanodex and Jacob et al.. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
-Cornelius et al. teaches that dantrolene is an effective inhibitor of IP3 and inhibits the release of calcium,
-Ryanodex teaches that dantrolene is an FDA approved drug, and
-More recently, Jacob et al. confirms Cornelius et al. that dantrolene inhibits mitochondrial Ca2+ uptake induced by IP3-mediated CA2+ release from the endoplasmic reticulum.
In order to expedite prosecution, the Examiner would like to address Applicants arguments pertaining to the previous 103 rejection.
In response to the previous 103 rejection, Applicants contend that Cornelius work focuses primarily on filamentous fungus, Neurospora crassa, which is not a mammal or human. Moreover, Applicants point out that other research that shows that dantrolene may not be able to inhibit IP3 inducted calcium release in mammals such as bovine. For example, Applicants point to Rossier whom discloses that “Neither dantrolene (200 WM) no 8-N-N-diethylamino)octyl-3,4,S-trimethoxybenzoate (10 MM) were able to abolish IP3-induced CA2+ release.”. In light of this, Applicants contend that a person of ordinary skill in the art would understand that dantrolene may or may not be “capable of blocking calcium release from the endoplasmic reticulum mediated by the IP receptor” in mammals.
In response to Applicants arguments, the Examiner appreciates Applicants for pointing out the work down by Rossier. However, the examiner recognizes that the work by Rossier was published in 1986 and as such would not necessarily be reflective of the knowledge in the art around the time of filing. For example, Jacob et al. (cited above) was published in 2014 and supports Cornelius et al. in showing that dantrolene inhibits mitochondrial Ca2+ uptake induced by IP3-mediated CA2+ release from the endoplasmic reticulum (ER) in striatal neurons prepared from rat embryos (page 9, Figure 1).
New Rejections Necessitated by Applicants amendments:
Claim(s) 1-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Glazner, Gordon (US2002/0107193, 2002-08-08) referred to herein as “Glazner” in view of Cornelius et al. (Biochemical and Biophysical Research Communications (1989) 162(2), 852-856), Ryanodex ® Label(revised on 7/2014) referred to herein as “Ryanodex” and Jacob et al. (Neuroscience Letters 2014; 575: 7-2), as applied to claims 1-12 above, in further view of Eagle Pharmaceuticals (WO2019/079721A1, 2019-04-25, IDS).
The applied reference has a common inventor/assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
The combination of Glazner in view of Cornelius et al., Ryanodex and Jacob et al., as set forth above and incorporated herein, suggest a method of treating HIV infection comprising administering an effective amount of a pharmaceutical composition comprising dantrolene to an individual in need of said treatment.
The combination differs from the instant claims in that it does not teach or suggest use of dantrolene prodrugs of the formula:
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.
Eagle Pharmaceuticals teaches that while dantrolene is the rescue agent of choice for the treatment of malignant hyperthermia (“MH”), it suffers from very poor solubility in water and high pH which make it unsuitable for subcutaneous or intramuscular administration (paragraphs 0005-0007). Accordingly, Eagle Pharmaceuticals teaches new formulations comprising prodrugs of dantrolene suitable for intramuscular or subcutaneous administration, wherein the prodrugs having the structure
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(paragraphs 0010-0011).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute dantrolene taught by the combination for a prodrug of dantrolene in view of the teachings of Eagle Pharmaceuticals. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
- Eagle Pharmaceuticals teaches new formulations comprising prodrugs of dantrolene which overcome the known incompatibilities for intramuscular or subcutaneous administration of dantrolene.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRANDON J FETTEROLF whose telephone number is (571)272-2919. The examiner can normally be reached M-F 6AM-4PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S Lundgren can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRANDON J FETTEROLF/Primary Examiner, Art Unit 1626