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 .
Priority
This application is a national stage application under 35 U.S.C. § 371 of
International Application No. PCT/US2020/044745, filed 08/03/2020, which claims the priority benefit of Application No. PRO62/883,295, filed 08/06/2019.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/10/2023 was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of Claims
Claims 1-30 are pending in this application. Claims 1, and 14-16 are amended. Claims 4-13 and 19 are withdrawn. Claims 1-3, 14-18 and 20-30 are currently under examination.
Applicant’s arguments, filed 09/03/2025, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. They constitute the complete set presently being applied to the instant application.
The obviousness rejection below is repeated from the 06/17/2025 Office Action and modified in order to address the most recent amendments.
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 of this title, 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 factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-3, 14-18 and 20-30 are rejected under 35 U.S.C. 103 as being unpatentable over Rothman (WO 2018/031216 Al) in view of Garovoy (WO 2013/003708 Al).
The instant claims are directed to a method of treating sexual dysfunction and increasing orgasmic ability, sexual satisfaction, desire in a female subject in need thereof wherein the dysfunction is female sexual interest/arousal disorder by orally administering 3,4-diaminopyridine (3,4-DAP or amifampridine) for at least 4 weeks.
Rothman et al. teach a method for treating sexual dysfunction in a subject in need thereof comprising topically administering a composition comprising a potassium channel blocker [0012]. Rothman teaches 3,4-diaminopyridine (3,4 DAP) as a particularly suitable potassium channel blocker [0023]. Rothman discloses the actual amount of the potassium channel blocker can depend on the patient's age, weight, sex, medical condition, disease or any other medical criteria and can be administered one or more times a day [0025]. Rothman discloses females as suitable subjects which are in need of increasing sexual arousal including menopausal and postmenopausal women [0043]. Rothman teaches enhancing sensitivity of cutaneous sensory afferent nerve endings by increasing the rate of peripheral nerve firing, increased neuronal sensitivity and should increase the probability of reaching orgasm [0059].
However, Rothman et al. fail to disclose administration of 3,4-diaminopyridine in an oral dose range of 9.5-189.5 mg comprising scored tablets in 3 or 4 doses per day as required by instant claim 28.
Garovoy et al. teach methods for treatment of any 3,4-diaminopyridine (3, 4 DAP) responsive disorder [0007]. Garovoy teaches 3,4 DAP can be used for treatment of motor neuron diseases including Parkinson’s disease by improving neuromuscular transmission and thus increasing the entry of cellular calcium which improves the acetylcholine in the nerve endings [0003]. Garovoy teaches an investigational product, dose, route regimen in where orally administering scored tablets of 10 mg amifampridine to subjects [000346]. Garovoy teaches a single dose study in the investigational product, dose, route regimen where the dose range of 3,4 DAP were 5-30 mg [000347]. Garovoy discloses 3,4 DAP phosphate salt is administered between 30-240 mg per day and 1-5 times per day [000142]. Garovoy discloses a therapeutically effective amount of 3, 4 DAP will vary depending on the condition to be treated, and can be readily determined by the treating physician based on improvement in desired clinical symptoms [00065].
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the claimed invention, to treat a sexual dysfunction in a patient in need thereof by orally administering a 14 day regimen of 3, 4 DAP following Rothman's disclosure of a treatment of sexual dysfunction of female sexual interest/arousal disorder in a subject by administering 3,4 DAP in combination with Garovoy’s method of administering 3, 4 DAP via 30-240 mg tablet administration because of the improved consistency of maximized oral bioavailability from one administration to the next. See MPEP 2144.05 Obviousness of Similar and Overlapping Ranges, Amounts, and Proportions.
A person of ordinary skill in the art would have been motivated to administer 3,4 DAP in tablet form to treat the sexual dysfunction of female sexual interest/arousal disorder to a subject in need thereof because of the accuracy in dosing and desirable bioavailability of an effective amount of 3,4 DAP. Given the combined teachings of Rothman and Garovoy, a skilled artisan would have a reasonable expectation of success in treating a patient with female sexual interest/arousal disorder by administering 3,4 DAP in an oral tablet dose 1-5 times a day. Therefore, based on the prior art of current record, the instantly claimed subject matter, taken as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the instant application was filed.
Response to Arguments
Applicant's arguments filed 09/03/2025 have been fully considered but they are not persuasive.
Applicant argues Rothman and Garovoy concern two completely different treatment methods (topical vs. oral) and that inventors surprisingly found subjects suffering from sexual dysfunction experienced overall improvement in their sexual functioning after daily oral administration of 3,4-DAPP.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, 3,4-diaminopyridine (3, 4 DAP) was taught by Rothman and Garovoy to improve the functioning of nerve endings with Rothman disclosing a result of increased probability of orgasm and treating low sex drive, sexual dysfunction, and the like, as well as menopausal and postmenopausal women and Garovoy disclosing methods of treating 3,4-DAP sensitive diseases, in a manner that improves or maximizes its efficacy, and/or improves or maximizes its oral bioavailability, and/or improves or optimizes the consistency of oral bioavailability from one administration to the next, and/or decreases the frequency or severity of adverse events. A person of ordinary skill would have had a reasonable expectation of success in treating a sexual dysfunction in a subject by administering an oral dose of 3, 4 DAP. See MPEP 716.02 Allegations of Unexpected Results.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant argues a person of ordinary skill in the art would not have been motivated to combine Rothman with Garovoy to administer 3,4-DAPP orally to treat sexual dysfunction with reasonable expectation of success without hindsight.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Conclusion
All claims are rejected, no claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNESTO VALLE JR whose telephone number is (703)756-5356. The examiner can normally be reached 0730-1700 M-F EST, 1st Friday off.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C Milligan can be reached at 571-270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/E.V./Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623