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 . Claims 1-2, 4-5, 7, 10-24 filed August 09, 2022 are currently pending. Claims 1, 10, 12 and 19 are independent.
Election/Restrictions
Applicant’s election without traverse of Group (II) claims 1-2, 4-5, 7, 11-17 and 19-23 in the reply filed on 11/10/2025 is acknowledged.
Claims 10, 18 and 24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 11/10/2025.
Secondly, Applicant’s election without traverse of biliary atresia as the species of fibrotic disease and dipyridamole as the species of phosphodiesterase inhibitor in the reply filed on 11/10/2025 is acknowledged.
Claim 12 is directed to the treatment or prevention of gastrointestinal fibrosis in a subject in need comprising administering a therapeutically effective amount of a phosphodiesterase inhibitor, while claim 19 is directed the treatment or prevention of liver and/or gallbladder fibrosis in a subject in need comprising administering a therapeutically effective amount of a phosphodiesterase inhibitor. Claim 20, which depends upon claim 19 discloses that the elected species of biliary atresia is a species of liver and/or gallbladder fibrosis. As such, claims 12-17 are also withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species of disorder, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/10/2025.
Priority
Acknowledgement is made of the national stage entry of PCT/CN2021/076307 filed 02/09/2021, which claims foreign priority to Application 202010084911.2 filed 02/10/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 08/09/2022 and 11/10/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112-Paragraph B
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 5, 11, 22 and 23 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 5 is directed to the method of claim 1 wherein the fibrotic disease is selected from fibrotic diseases of liver, gallbladder, lung, kidney, bladder, heart, blood vessel, eye, skin, pancreas, gastrointestinal, bone marrow, penis, breast, and muscle; preferably, the fibrotic disease is selected from fibrotic diseases of liver, gallbladder, lung and gastrointestinal.
Regarding claim 5, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). This situation is duplicated in claims 11, 22 and 23.
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 –
(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) 1-2, 4-5, 7, 19-21, 23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Saito (Hepatology Research Vol. 44 pages 460-473 published 2014).
Claim interpretation is as follows. Claim 1 is directed to the method of preventing and/or treating a fibrotic disease comprising administering a therapeutically effective amount of a PDE inhibitor or a pharmaceutically acceptable salt thereof to a subject in need thereof. Claim 19 is directed to the method of preventing and/or treating a fibrotic disease of the liver and or gallbladder comprising administering a therapeutically effective amount of a PDE inhibitor or a pharmaceutically acceptable salt thereof to a subject in need thereof. As disclosed in page 12 of the instant specification, treatment of mammalian patients such as a mouse, rat or rabbit comprising said fibrotic disorder reads on the treatment of a subject in need thereof.
Saito (Hepatology Research Vol. 44 pages 460-473 published 2014) teaches the method of treating hepatic fibrosis in a subject in need comprising orally administering a therapeutically effective amount of the phosphodiesterase-type-3 inhibitor cilostazol to the afflicted subject in a carbon tetrachloride induced animal model (abstract). As shown in Figures 1, 2, 4 and 5, said oral administration of the therapeutically effective amount of cilostazol in a solid powder (food pellet) effectively reduced fibrosis in the liver of the afflicted patient (Figure 2), reduced the expression of hepatic fibrosis biomarkers of smooth muscle actin in the liver of the afflicted patient (Figure 4) and suppressed the proliferation and activation of hepatic stellate cells in the liver of the afflicted patient (Figure 5).
Claim(s) 1-2, 5, 7, 19, 20, 23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Said (Can. J. Physiol. Pharmacol. Vol. 91 pages 1055-1063 published 2013).
Said (Can. J. Physiol. Pharmacol. Vol. 91 pages 1055-1063 published 2013) teaches the method of treating and reversing liver fibrosis in a thioacetamide induced hepatic fibrosis patient comprising administration of a therapeutically effective amount of the art-recognized phosphodiesterase-type 5 inhibitor sildenafil (abstract, page 1055). Said sildenafil was intraperitoneally administered in a dose of 10 mg/kg, 3 times a week for 8 weeks (page 1056 right col.). As shown in Tables 6 and 15, administration of said phosphodiesterase type 5 inhibitor resulted in the reduction of extensive scarring and fibrosis in the afflicted patient (pages 1056-1058 right col., Table 15, Figures 2A-2D).
Claim(s) 1-2, 4-5, 7, 19-21, 23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wanless (Hepatology Vol. 24 pages 855-864 published 1996).
Wanless (Hepatology Vol. 24 pages 855-864 published 1996) teaches the method of treating hepatic fibrosis in a subject in need comprising oral administration of the elected phosphodiesterase inhibitor dipyridamole in a dose of 25 mg, twice a day as a tablet to the afflicted cholesterol and stilbestrol-induced hepatic fibrosis patient (abstract, page 856 left col., page 862 right col., Table 1 ). As shown in Table 3, dipyridamole treated patients comprised a reduction in hepatic sinusoidal fibrosis, and reduction of liver hydroxyproline content, (page 858, page 862).
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.
Claim(s) 1-2, 5-6, 11, 19-20, 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over Naef (WO2017/085056 published 05/26/2017).
Naef teaches compounds of Formula (I) as potent inhibitors of phosphodiesterase type 5 (PDE-5) (abstract, page 1 lines 1-12, page 8 lines 20-35, claims 1, 10). Naef teaches that said PDE-5 inhibitors comprise greater potency at inhibiting phosphodiesterase type 5 compared to the art-recognized PDE-5 inhibitors sildenafil or dipyridamole (page 8 lines 20-35, page 107).Treatment of liver fibrosis in a subject in need comprising administration of said PDE-5 inhibitor is embraced within the teachings of Naef (page 37 lines 1-20, claims 1, 10-11). Treatment of adult human patients and administration of said PDE-5 inhibitor via oral and parenteral routes are also embraced within the methodology of Naef (page 42 lines 1-15).
Therefore, one of ordinary skill in the art prior to the time of the invention would have found it prima facie obvious to select a PDE-5 inhibitor of Formula (I) of Naef and administer said compound to treat hepatic fibrosis in a subject in need, arriving at the presently claimed methodology. Applicant is reminded that “[I]t is well settled that it is a matter of obviousness for one of ordinary skill in the art to select a particular component from among many disclosed by the prior art as long as it is taught that the selection will result in the disclosed effect, even when the possible selections number 1200 or in the thousands. Merck & Co., Inc. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989); In re Corkill, 771 F.2d 1496, 1500 (Fed. Cir. 1985).” Applicant is also reminded of MPEP 2144.07 wherein the selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945). In the instant case, liver fibrosis is one of thirty three disorders taught by Naef to be effectively treated with the administration of a therapeutically effective amount of a PDE-5 inhibitor. Accordingly, said skilled artisan would have readily predicted that administration of a PDE-5 inhibitor of Naef to a patient with hepatic fibrosis would have effectively treated the afflicted subject.
It is noted that Naef does not specifically teach wherein the patient is treated in a dose of 0.1-100 mg/kg per day and said PDE-5 inhibitor is administered once or multiple times per day (claims 11, 22). However, the optimum dose and dosing cycle of the PDE-5 inhibitor to the patient comprising hepatic fibrosis would have been a matter well within the insight of one of ordinary skill in the art. Such a determination would have been made in accordance with a variety of factors, such as the route of administration, pharmacological considerations, such as activity, efficacy, pharmacokinetics and toxicology profiles of the combined regimen, as well as the age, weight, sex, diet and severity of the medical condition of the patient, as disclosed by Naef (pages 41-42). Thus, the dose and dosing cycle that would have been employed would have varied widely and, in the absence of evidence to the contrary, the current claimed specific administration regimen is not seen to be inconsistent with one that would have been determined by the skilled artisan. Furthermore, absent and evidence demonstrating a patentable difference between the compositions administered and the criticality of the claimed dose and dosing cycles, the determination of the optimum or workable frequency of administration given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II)(A) and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)(”[W]here the general conditions of the claim are disclosed in the prior art, it is not inventive to discover the workable ranges by routine experimentation.”
Conclusion
In view of the rejections set forth above, no claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GEORGE W KOSTURKO whose telephone number is (571)270-5903. The examiner can normally be reached M-F 9:00-5:30.
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/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621