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
In the amendment filed March 24, 2026, claim 1 is amended. Claims 1, 5-11, and 13-25 are currently pending, with claims 19-25 being previously withdrawn.
Response to Arguments and Amendment
Rejections for Indefiniteness:
In the Remarks submitted on March 24, 2026, Applicant asserts that the scope of claim 1 is clear, both because the method does not require that one actually measure hepatotoxicity and also because various means of measuring hepatotoxicity are known in the art (pg. 7 of Applicant’s remarks, first full paragraph). These arguments have been fully considered but are not found persuasive.
While it is true that the method, as claimed, does not include a step of measuring hepatotoxicity, it is regardless the case that, as the claim is currently recited, hepatotoxicity would necessarily have to have been measured in order to know whether the claim had been practiced. But more to the point, the claim does not define increased hepatotoxicity sufficiently, in terms of how it must be measured, or how it is quantitatively defined, to enable one of skill in the art to determine whether the method had been practiced, regardless of what hepatic measurements may have been made. It would be unclear whether a determination of no “increased hepatotoxicity” must be made in the actual subject of the method, whether it must be determined by a conventional clinical trial with statistical analysis, whether a histological examination of a small number of mice as in the instant disclosure is sufficient, or whether some other means of determining “increased hepatotoxicity” is suitable. Furthermore, hepatotoxicity can be measured in a variety of ways, using a variety of biomarkers and a variety of thresholds, and they would not all necessarily give the same answer as to whether an increase in hepatotoxicity had occurred. For example, in a clinical trial, one could define hepatotoxicity by increases in various liver enzymes, and quantify it by different percentages of subjects who received combination therapy having increased liver enzyme levels increased by a particular fraction over the upper normal limit of a subjects who received monotherapy. Just within this one variation, the outcome would depend on the defined enzymes and thresholds.
Applicant further notes that the specification provides a proof of concept. This presumably refers to data in the instant specification suggesting that the livers of mice receiving elacridar + riluzole did not show greater pathology than the livers of mice receiving riluzole alone, as determined by histological examination. It would be unclear however whether this is the standard to which instant claim 1 refers. This evaluation obviously would not be applied to the actual subject of the method. If claim 1 is intended to require that the combination therapy does not cause increased hepatotoxicity relative to monotherapy, as evaluated by histological examination of similarly treated mice, that should be clarified. Otherwise, it is unclear what the recitation requires.
Finally, Applicant notes that claim 1 has been amended to recite that the method does not result in increased hepatotoxicity relative to administration of the drug at the same dose in the absence of inhibitor. While this provides a degree of additional clarification, it does not fundamentally address the indefiniteness, described above, relating to how “increased hepatotoxicity is defined and determined.
For these reasons, the rejections for indefiniteness are maintained.
Rejections for nonstatutory double patenting:
Applicant asserts that the rejections for nonstatutory double patenting are overcome by the filing of terminal disclaimers over the reference patents. However, there is no record in the file of such terminal disclaimers having been submitted. As such, the rejections for nonstatutory double patenting are maintained.
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.
Claims 1, 5-11, and 13-18 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.
Claim 1 is indefinite for reciting, “wherein the method does not result in increased hepatotoxicity relative to administration of the drug at the same dose in the absence of the inhibitor,” because a person of ordinary skill in the art could not reasonably determine the metes and bounds of this limitation. It would be unclear how one would determine whether any given administration of drug and inhibitor met this functional limitation. For example, it is unclear whether this limitation requires
a showing that the method does not result in increased hepatotoxicity relative to administration of the drug alone, for each individual subject of the method;
a clinical trial showing that, within defined dosage limits, the method normally does not result (or never results) in increased hepatotoxicity relative to administration of the drug in a species of interest (presumably human);
some or any evidence from any mammal, suggesting that the method does not result in increased hepatotoxicity relative to administration of the drug alone; or
some other showing.
The instant specification discloses a histological examination of a liver section from a mouse that received administration of elacridar and riluzole, in comparison to a histological examination of a liver section from another mouse that was administered only riluzole as evidence that coadministration of riluzole and elacridar was not hepatotoxic relative to administration of riluzole alone (pg. 34, lines 6-8 and Fig. 3D). Presumably, such an analysis is not required on the individual subject of the claimed method in order to determine whether the element pertaining to hepatoxicity is met (possibility (i), above) although such an analysis could potentially be made by other methods. It is equally unclear whether the mouse study described in the specification is meant to show that the hepatotoxicity criterion is satisfied for all coadministrations of riluzole+elacridar, in all species, or whether it is intended that a clinical study in humans, for example, showing typical hepatotoxicity at various doses would establish the criteria for the discussed element, in humans. In short, the meaning and requirements of this element are unclear. Claims 5-18 are indefinite for depending from claim 1 without curing this indefiniteness.
Double Patenting Rejections
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, 5-11, and 13-18 are subject to a nonstatutory double patenting rejection over the ’615 patent:
Claims 1, 5-11, and 13-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 10,258,615 to Trotti et al. (“the ’615 patent”). Although the claims at issue are not identical, they are not patentably distinct from each other because they claim inventions of nearly identical and broadly overlapping scope.
In the
Instant claim 1 recites, inter alia, a method of treating a neurodegenerative disease, the method comprising co-administering a drug that is also a substrate of an ABC transporter, and an ABC transporter inhibitor, resulting in treatment or amelioration of the disease. Claim 1 of the ’615 patent recites identical subject matter, except that the neurodegenerative disease is limited to one of two specific diseases. Instant claim 2 limits the neurodegenerative disease to one of several recited diseases, including the two of claim 1 of the ’615 patent. Instant claims 5-6, 9, 10, and 18 are identical to claims 3-6 and 9 of the ’615 patent. The limitations of instant claims 11 and 13 are included in claims 7 and 9, respectively, of the ’615 patent.
Instant claim 7 recites that the drug and/or inhibitor is part of a pharmaceutical composition. At pg. 12, lines 11-13, the instant specification states that the phrase “pharmaceutical composition” means the active compound is mixed with a pharmaceutically acceptable carrier. At pg. 21, line 31 to pg. 22 line 5, the instant specification states that such a carrier can be a solvent such as water, ethanol, or a polyol, a surfactant, and other carriers. Claim 10 of the ’615 patent recites that the drug can be administered intravenously, which would require that the drug be combined with a solvent. As such, instant claim 7 is an obvious variant of claims 1 and 10 of the ’615 patent.
Instant claim 8 recites that the composition comprises an extended-release formulation. This is an obvious variant of the drug for administration via inhalational, oral, rectal, etc. administration routes of claim 10 of the, because extended-release formulation for various administration routes are extremely common in the art. See for example the non-patent publication, Extended Release Formulation: An Overview, Pharma Sci. Monitor, 4, pgs. 3522-3534 (2013) by Patil et al., which states “controlled release drug delivery has become the standards [sic] in the modern pharmaceutical design…” and “oral extended release drug delivery medication will continue to account for the largest share of drug delivery systems” (Abstract).
Instant claims 14 and 15 recite wherein the mammal receiving administration has improved survival and delayed disease progression, respectively. While such intended results generally do not carry patentable weight, as discussed further below, these are nonetheless obvious variants of the element of claim 1 of the ’615 patent that the neurodegenerative disease is treated or ameliorated by the administration, i.e. obvious manners in which the disease would be treated or ameliorated are increased survival time and delayed disease progression.
Instant claim 16 specifies that the mammal is a rodent or primate and instant claim 17, depending from claim 16, specifies that the primate is human. These are well-known examples, and obvious variants, of mammals, a mammal being the recipient of treatment in claim 1 of the ’615 patent. Moreover, it was well known that human treatment is the ultimate goal of most pharmaceutical development, and that rodent models were commonly used in testing of pharmaceutical candidates (see, e.g. the non-patent publication, Transgenics, toxicity and therapeutics in rodent models of mutant SOD1-mediated familial ALS, Prog. Neurobiol., 85, pgs. 94-134 (2008) by Turner et al.). As such, claims 16 and 17 are obvious variants of claim 1 of the ’615 patent.
Claims 1, 5-11, and 13-18 are subject to a nonstatutory double patenting rejection over the ’596 patent:
Claims 1, 5-11, and 13-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,369,596 to Trotti et al. (“the ’596 patent”). Although the claims at issue are not identical, they are not patentably distinct from each other because they claim inventions of nearly identical and broadly overlapping scope.
Instant claim 1 is identical to claim 1 of the ’596 patent, with the exception that the latter specifies that the neurodegenerative disease drug is one of several well-known species of such drugs.
Instant claim 5 recites a list of specific neurodegenerative disease drugs, a list that includes all the drugs recited in claim 1 of the ’596 patent, plus a few additional well-known drugs. Instant claim 6 and the ’596 patent claim 4 recite the same feature of specific ABC inhibitors. Instant claims 6-10 and 14-18 recite the same features as do claims 4-8 and 12-16 of the ’596 patent. The recitations of instant claims 11 and 13 are recited by claims 9 and 11 of the ’596 patent.
Conclusion
This Action is Non-Final because it includes rejections that could have been made in the previous Office Action. Namely, the Examiner previously forgot to reiterate the non-statutory double patenting rejections described above.
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 extension fee 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 ALEXANDER K SHOWALTER whose telephone number is (571)270-0610. The examiner can normally be reached M-F 9:00 am to 5:00 pm, eastern time.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S Lundgren can be reached on (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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/ALEXANDER K. SHOWALTER/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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