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
The instant application is a CON of the following applications:
19/390,174 filed on 11/14/2025
19/244,143 filed on 06/20/2025
16/607,252 filed on 10/22/2019
The instant application is a 371 of PCT/US2018/028885 filed on 04/23/2018, and claims priority to provisional application 62/489,016 filed on 04/24/2017.
Status of the Claims
Per Applicant’s amendment to the claims, submitted on 04/14/2026, claim 1 is amended. Currently, claims 1-30 are pending in the instant application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/06/2026 and 05/19/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restrictions
In response to the requirement for Species Election, submitted on 04/07/2026, Applicant has elected the following species of 5HT3 antagonist:
Ondansetron
The above species has been elected without traverse, and reads on claims 1-14, 23, and 24. Accordingly, claims 15-22 and 25-30 are withdrawn from consideration. Claims 1-14 and 23-24 are pending examination.
Claim Rejections - 35 USC § 112 – Second Paragraph
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.
Claim 4-13 and 24 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 4 is indefinite for reciting “comprising administering pramipexole dihydrochloride monohydrate”, because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. The recitation makes it unclear whether the recited “pramipexole dihydrochloride monohydrate” is a separate entity from the pramipexole recited in claim 1. This rejection may be overcome by a re-wording of the claim (i.e., “wherein the pramipexole is pramipexole dihydrochloride monohydrate”, etc.).
Claims 5-13 are indefinite for reciting the method of claim 1 “comprising administering the patient a daily dose of […] pramipexole dihydrochloride monohydrate”, because a person of ordinary skill in the art would not reasonably understand the metes and bounds of the claim. The current recitation of the indicated claims makes it unclear whether the “pramipexole dihydrochloride monohydrate” is a separate entity from the pramipexole recited in claim 1. These rejections may be overcome by either a re-wording of each of the claims (i.e., “wherein the pramipexole is pramipexole dihydrochloride monohydrate”, etc.), or shifting the claim dependency such that the claims depend on claim 4.
Claim 24 is indefinite for reciting “comprising administering ondansetron hydrochloride dihydrate”, because a person of ordinary skill in the art would not reasonably understand the metes and bounds of the claim. The current recitation of the indicated claim makes it unclear whether the “ondansetron hydrochloride dihydrate” is a separate entity from the ondansetron recited in claim 23. This rejection may be overcome by a re-wording of the claim (i.e., “wherein the ondansetron is ondansetron hydrochloride dihydrate”, etc.).
Claim Rejections - 35 USC § 112 – First Paragraph
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1 and 14 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for administering a combination of ondansetron and pramipexole, does not reasonably provide enablement for a combination of any 5HT3 antagonist and pramipexole. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make use of the invention commensurate in scope with these claims.
Looking towards Applicant’s disclosure with regards to claim 1, the specification provides a working example on pages 39-44 indicated as Example 1. Example 1 details a phase I study wherein subjects were administered pramipexole dihydrochloride monohydrate alone, or in combination with ondansetron hydrochloride dihydrate (specification page 39)1. The objective of said study being to assess whether ondansetron could safely attenuate gastrointestinal side effects of pramipexole. The instant claim recites the administration of a 5HT3 antagonist, and under broadest reasonable interpretation, this would encompass all compounds capable of antagonizing 5HT3. The disclosure, as provided, is not sufficient to support the wide breadth of the claim, as “5HT3-antagonist” may encompass compounds materially different from the exemplary ondansetron.
Likewise, in regards to claim 14, the specification is not commensurate with the scope of the claim in that the provided working example is not sufficient to support each of alosetron, azasetron, dolasetron, granisetron, palonosetron, ramosetron, or troposetron. While each of the recited compounds is considered as a 5HT3 antagonist, they are also distinct compounds from the tested ondansetron, and ondansetron alone cannot be considered as representative of all the species presented.
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 1-14 and 23-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 12648934 (herein the ‘934 patent). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the application and the claims of the issued patent are exceedingly overlapping in scope and are directed to the same subject matter.
Claim 1 of the instant application recites a method for treating a patient suffering from major depressive disorder (MDD), comprising administering to the patient a daily dose of 1 µg to 300 mg of a 5HT3-antagonist, or a pharmaceutically acceptable salt or solvate thereof and a daily dose of 0.125 mg to 20 mg of pramipexole, or a pharmaceutically acceptable salt or solvate thereof.
Claim 1 of the ‘934 patent recites a method for treating a patient suffering from major depressive disorder (MDD), comprising administering to the patient a daily dose of 6 mg to 64 mg of ondansetron, or a pharmaceutically acceptable salt or solvate thereof, and a daily dose of 0.125 mg to 20 mg of pramipexole, or a pharmaceutically acceptable salt or solvate thereof.
As can be seen from the claims above, both the invention of the instant application and the ‘934 patent are directed towards the treatment of MDD by administering to a patient a combination of a 5HT3 antagonist and pramipexole. While the instant claim more broadly claims the use of a 5HT3 antagonist, dependent claims 14, 23, and 24 recite wherein said antagonist is ondansetron, which overlaps with recited ondansetron in the claim of the ‘934 patent. While the recited range amounts for the 5HT3 antagonist may differ between the claims of the instant application and the ‘934 patent, it still remains that the claim of the issued patent falls squarely within the scope of the claim of the instant application. Accordingly, the inventions of the instant application and the ‘934 patent cannot be considered as patentably distinct from one another.
Claims 1-14 and 23-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 12521374 (herein the ‘374 patent). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the application and the claims of the issued patent are exceedingly overlapping in scope and are directed to the same subject matter.
Claim 1 of the instant application recites a method for treating a patient suffering from major depressive disorder (MDD), comprising administering to the patient a daily dose of 1 µg to 300 mg of a 5HT3-antagonist, or a pharmaceutically acceptable salt or solvate thereof and a daily dose of 0.125 mg to 20 mg of pramipexole, or a pharmaceutically acceptable salt or solvate thereof.
Claim 1 of the ‘374 patent recites a method for treating a patient suffering from major depressive disorder, comprising administering to the patient a daily dose of 1 μg to 300 mg of ondansetron, or a pharmaceutically acceptable salt or solvate thereof, and a daily dose of about 0.5 mg to about 6 mg of pramipexole, or a pharmaceutically acceptable salt thereof.
As can be seen from the claims above, both the invention of the instant application and the ‘374 patent are directed towards the treatment of MDD by administering to a patient a combination of a 5HT3 antagonist and pramipexole. While the instant claim more broadly claims the use of a 5HT3 antagonist, dependent claims 14, 23, and 24 recite wherein said antagonist is ondansetron, which overlaps with recited ondansetron in the claim of the ‘374 patent. Furthermore, while the range amount for pramipexole differs between the claim of the instant application and the claim of the ‘374 patent, the range recited in the ‘374 patent falls squarely within the bounds of the instant application. As the instant application and the issued patent are essentially directed towards treating the same disease by administering a combination of the same component actives, they cannot be considered as patentably distinct from one another.
Allowable Subject Matter
While the claims are not currently in allowable condition, they do contain allowable subject matter. More specifically, the treatment of MDD by administration of a combination of ondansetron and pramipexole. The closest prior art found is Bryson (US 20130225626 A1).
Bryson teaches sublingual compositions comprising dopamine agonists for the treatment of depressive disorders. Among the dopamine agonists indicated for use by Bryson is pramipexole (specification [0017])2. Bryson further indicates the inclusion of apomorphine for the amelioration of adverse effects, in combination with an anti-emetic such as ondansetron (specification [0145])3. While the teachings of Bryson are relevant to the subject matter of the instant claims in that they indicate both pramipexole and ondansetron, Applicant has provided a declaration in support of unexpected effects regarding the combination of said components.
The declaration has been included in the Information Disclosure Statement, and has been previously submitted in parent applications 16/607,252 and 19/244,143. The declaration penned by Dr. Kathleen E. Clarence-Smith alleges unexpected results when administering ondansetron alongside pramipexole. Dr. Smith indicates that it would not have been expected that (i) 5HT3 antagonists would be capable of ameliorating nausea and vomiting caused by dopamine receptor agonists, and that (ii) co-administration of 5HT3 antagonists and dopamine receptor agonists were known to cause deadly adverse events (Declaration page 3)4.
With regards to element (i), Dr. Smith makes reference to Hoffman (Am J Ther. 2003 Nov-Dec; 10(6): 447-51) and Andrews (Eur. J. Cancer. 1993) which indicate that ondansetron as a 5HT3 antagonist would be expected to only be effective in treating nausea and vomiting associated with 5HT3 receptor activation (Declaration page 6). In the case of pramipexole, Dr. Smith indicates, that because pramipexole is a dopamine receptor agonist with a mechanism of action distinct from 5HT3. It is further indicated that the Andrews reference provides testing of co-administration of 5HT3 anti-emetics and apomorphine (a dopamine agonist like pramipexole), and indicates that emesis caused by apomorphine was unaffected by 5HT3 antagonists. Accordingly, the Declaration demonstrates that there would not have been an expectation, prior to the instant invention, that ondansetron would have been effective in treating pramipexole induced emesis.
With regards to element (ii), the declaration presents the label information for the pharmaceutical product APOKYN (i.e., apomorphine). The label indicates that apomorphine is a dopamine agonist, causes adverse effects including nausea and vomiting, and is contraindicated for use with 5HT3 antagonists, including ondansetron (Declaration page 9). Per said label, Dr. Smith indicates that the combination of dopamine agonist and 5HT3 antagonist would have been expected to produce “profound hypotension and loss of consciousness” as opposed to the results presented in the disclosure wherein ondansetron was capable of ameliorating nausea and vomiting associated with pramipexole administration.
Accordingly, the evidence presented by Applicant in the submitted documents of the IDS establishes nonobviousness of the method of the instant claims, at least with regards to the combination of ondansetron and pramipexole.
Conclusion
Claims 1-14 and 23-24 are rejected.
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/ERIC TRAN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 “A Phase I study was conducted in subjects receiving a single oral dose of pramipexole dihydrochloride monohydrate ("pramipexole") with or without a single oral dose of ondansetron hydrochloride dihydrate ("ondansetron").”
2 “The invention features a pharmaceutical composition in unit dosage form formulated for sublingual administration, the unit dosage form having a first portion including an acid addition salt of a dopamine agonist, and a second portion including a pH neutralizing agent, wherein the dopamine agonist is selected from bromocriptine, cabergoline, dihydroergocryptine, lisuride, piribedil, pergolide, pramipexole, rotigotine, ropinirol, and acid addition salts thereof. In particular embodiments, the unit dosage form is a lozenge, a pill, a tablet, a film, or a strip.”
3 “Potential adverse effects can be ameliorated by administering apomorphine, or an apomorphine prodrug, in combination with an anti-emetic agent, such as nicotine, lobeline sulfate, pipamazine, oxypendyl hydrochloride, ondansetron, buclizine hydrochloride, cyclizine hydrochloride, dimenhydrinate, scopolamine, metopimazine, benzauinamine hydrochloride or diphenidol hydrochloride. In certain instances it may be desirable to incorporate the anti-emetic into the sublingual formulation for simultaneous administration in combination with apomorphine, or apomorphine prodrug.”
4 “5HT3 receptor antagonists (e.g., ondansetron) can be safely co-administered with pramipexole to increase tolerance to pramipexole, which allows depressed subjects to receive effective doses of pramipexole that were otherwise unachievable. This was also surprising for at least the following reasons: (i) 5HT3 receptor antagonists were not known to, and I would not have been expected 5HT3 to, suppress nausea and vomiting caused by a dopamine receptor agonist given the different mechanisms of action; and (ii) co-administration of a 5HT3 receptor antagonist with a dopamine receptor agonist was well known to cause severe and potentially deadly adverse events. Indeed, the FDA contraindicated coadministration of 5HT3 receptor antagonists with the dopamine receptor agonist, apomorphine, which is also mentioned in the same list as pramipexole in Bryson, a reference cited by the Office.”
Prosecution Insights