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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 69-86 in the reply filed on September 22, 2206 is acknowledged.
Claims 87 and 88 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on September 22, 2026.
Information Disclosure Statement
The information disclosure statement filed November 14, 2024 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered. Specifically non-patent literature number 15 is not found. A 4-page translation document dated March 19, 2025 has been filed, and if this is the document Applicant may correct the listing as appropriate.
Claim Rejections - 35 USC § 112
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 69-74 and 80-85 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 increasing peak VO2 at maximum effort of patients between about 12 years old and under about 18 years old who had undergone Fontan surgery by administering udenafil or a salt thereof at a total daily dose of about 125 mg - 175 mg, it does not reasonably provide enablement for treating patients of any age.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with claims 31-40 as recited. “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation.” MPEP § 2164301(a) (citing In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)).
Applicant’s disclosure may be enabling for increasing peak VO2 at maximum effort of patients between about 12 years old and under about 18 years old who had undergone Fontan surgery by administering udenafil or a salt thereof at a total daily dose of about 125 mg-175 mg, which indicates increasing the patient’s exercise capacity. That is one aspect of treating such a patient. However it does not reasonably provide enablement for treating patients of any age who had undergone Fontan operation.
In re Wands, 858 F.2d 731, 736-40, 8 USPQ2d 1400, 1403-07 (Fed. Cir. 1988), set forth eight factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." (MPEP § 2164.01 (a))
a. The breadth of the claim: The rejected claims are drawn to methods of treating a single ventricle heart disease (SVHD) patient by administering a total daily dose of about 125mg-175 mg of udenafil or a pharmaceutical acceptable salt thereof.
b. Nature of the invention: The nature of the invention is methods of treating patients of SVHD in those who had undergone a Fontan surgery, by administering about 125mg-175 mg daily total dose of udenafil or a pharmaceutical acceptable salt thereof in a treatment regimen and/or with daily administration.
c. The state of the prior art: Goldberg reported that sildenafil, another phosphodiesterase (PDE)-5 inhibitor, significantly improved ventilatory efficiency during peak and submaximal exercise. (Goldberg, D.J., et al., Impact of Oral Sildenafil on Exercise Performance in Children and Young Adults After the Fontan Operation—A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial, Circulation, 123:1185-1193 (2011)). There was also an indication that at anaerobic threshold oxygen consumption was improved in two subgroups, suggesting that sildenafil may improve exercise performance in children and young adults with single-ventricle physiology after the Fontan operation. Rychik (US 2005/0272741) teaches methods for “treating a pediatric patient in need of improved cardiac performance comprising the administration of sildenafil (or vardenafil or tadalafil), said method being effective to improve cardiac function” (claims 1, 6; see title; abstract; paras. 0002, 0012-59).
d. Level of one of ordinary skill in the art: the level of ordinary skill is high as trained physicians would manage patients of SVHD.
e. Level of predictability in the art: the level of predictability in SVHD treatment, including among those who had undergone a Fontan procedure, would be low as the type and severity of SVHD, and presence of any additional morbid conditions or complications would differ widely among individual patients. For instance as Applicant notes (see parent application 16/146762, Remarks, 9-10, February 19, 2020), use of sildenafil in children, despite Goldberg’s findings discussed above, is not recommended due to its potential risks.
f. Amount of direction provided by the inventor: The disclosure does not provide direction on how to treat any and all symptoms of SVHD, or improving exercise capacity at by peak VO2 and at anaerobic threshold, in patients of any age other than adolescents who had undergone a Fontan procedure. Udenafil, as a PDE-5 inhibitor, would be expected to reduce pulmonary vascular resistance resulting from a Fontan physiology (paras. 0071, 0092-100, pre-grant publication US 2019/0030037). However whether the reduction leads to improving exercise capacity, treatment of symptoms of SVHD, or the underlying condition itself, in patients of any age who has undergone a Fontan procedure has not been contemplated. Applicant’s clinical data does not support improvement of “exercise capacity” as a categorical, undefined parameter of cardiac performance in SVHD patients.
g. Existence of working examples: The disclosure contains limited data tending to support clinical attainment of improving exercise capacity as indicated by peak VO2 at maximum effort. Applicants disclose exercise testing via peak VO2 values during maximal effort or at anaerobic threshold (para. 0074, US 2019/0030037). Applicant’s disclosure supports that over a time period of 5 days, the test subjects’ peak VO2 at maximal effort increased modestly for the 87.5 mg twice daily group. Peak VO2 at anaerobic threshold decreased for the same group, however.
h. Quantity or experimentation needed to make or use the invention based on the content of the disclosure: considering the state of the art as discussed by the references above, particularly regarding the unpredictability of treating wide ranging side effects and disease states of SVHD, and the lack of guidance provided in the specification, the person of ordinary skill at the time of filing would have to engage in significant amount experimentation and ingenuity to practice the invention commensurate in the scope of the claims.
In conclusion, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with claims 69-74 and 80-85.
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 69-86 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4-6 of U.S. Patent No. 10137128.
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to a method of treating an adolescent with single ventricle heart disease for improving the adolescent's exercise capacity after Fontan palliation, as determined by maximum oxygen uptake at maximum exercise output (VO2 measurement), said method comprising: orally administering to the adolescent in accordance with a treatment regimen an oral dosage form comprising an effective dose of udenafil, or a pharmaceutically acceptable salt thereof, to improve the adolescent's VO2 measurement, wherein the adolescent has undergone Fontan surgery, wherein the human adolescent is between about 12 years old and under about 18 years old, and wherein the total daily dose of udenafil, or a pharmaceutically acceptable salt thereof, is from about 125 mg to about 175 mg. The ’128 patent claims further recite increasing the likelihood of improving the adolescent's exercise capacity as an alternative to improving the adolescent's exercise capacity, and therefore the present claims are encompassed by the ‘128 patent’s claims.
Claims 69-86 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4-6, 10-12, and 18-22 of U.S. Patent No. 10653698.
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to a method of treating a patient born with functional single ventricle congenital heart disease who has undergone Fontan palliation for improving the patient's exercise capacity wherein exercise capacity is determined by maximum oxygen uptake at maximum exercise output (VO2 measurement), said method comprising: orally administering to the patient in accordance with a treatment regimen an oral dosage form comprising an effective dose of udenafil, or a pharmaceutically acceptable salt thereof, to improve the patient's VO2 measurement, wherein the patient has undergone Fontan surgery, wherein the human patient is between about 12 years old and about 18 years old, and wherein the total daily dose of udenafil, or a pharmaceutically acceptable salt thereof, is from about 125 mg to about 175 mg. The ’698 patent claims further recite increasing the likelihood of improving the adolescent's exercise capacity as an alternative to improving the adolescent's exercise capacity, and therefore the present claims are encompassed by the ‘698 patent’s claims.
Claims 80-86 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 6-9 of U.S. Patent No. 12048701.
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to a method of treating a single ventricle heart disease (SVHD) patient with udenafil, or a pharmaceutically acceptable salt thereof, to improve the SVHD patient's exercise capacity at both the patient's VO2 max and anaerobic threshold, wherein the SVHD patient has undergone Fontan palliation, said method comprising: administering to the SVHD patient an effective daily dose of udenafil, or a pharmaceutically acceptable salt thereof, to treat the SVHD patient to improve the SVHD patient's exercise capacity at both VO2 max and the anaerobic threshold, wherein the udenafil, or a pharmaceutically acceptable salt thereof, is administered in a total daily dose of about 175 mg of udenafil, or a pharmaceutically acceptable salt thereof. The present claims recite a dose range of about 125 mg to about 175 mg of udenafil or a pharmaceutically acceptable salt thereof, however this range includes the about 175 mg in the ‘701 patent’s claims.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to H. S. PARK whose telephone number is (571)270-5258. The examiner can normally be reached on weekdays.
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H. SARAH PARK
Primary Examiner
Art Unit 1614
/H. SARAH PARK/Primary Examiner, Art Unit 1614
