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
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. CN-2023105795396, filed on 05/22/2023.Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Status of Claims
Claims 11-16 are pending and under examination
Any rejection found in the previous Office Action and not presented herein has been
withdrawn based upon Applicant’s amendments.
Response to Amendments
Applicant’s amendments to the claims of March 2, 2026, in response to the Office Action of December 10, 2026, are acknowledged.
Response to Arguments
Applicant’s arguments are directed towards the claims, as amended, which are addressed in the new rejection set forth below. Applicant’s allegations of unexpected results are not unexpected as compared to the closest prior art set forth below.
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 11-16 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 a method of treating liver fibrosis by administering sotalol in a subject in need thereof, wherein the subject already has liver fibrosis prior to treatment, does not reasonably provide enablement for treating or inhibiting liver fibrosis by administering sotalol, to any and all subjects, with or without liver fibrosis present. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01(A)). These include: nature of the invention, breadth of the claims, guidance of the specification, the existence of working examples, state of the art predictability of the art and the amount of experimentation necessary. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the Invention: The nature of the invention is complex in that claims 11-16 are drawn to a method of treating or inhibiting liver fibrosis by administering sotalol to a subject. However, subject is not defined, and as currently claimed can be construed as any person or animal with or without liver fibrosis. Further, inhibition is not defined and can be construed as a reduction of already present liver fibrosis, or prevention altogether in a subject that does not already have liver fibrosis, which is undeterminable and not a guaranteed outcome.
Breadth of the Claims: The claims are broad in that the claims recite a method for treating or inhibiting liver fibrosis in a subject by administering sotalol to the subject, wherein the subject is any and all humans or animals, either with or without present liver fibrosis.
The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims.
Guidance of the Specification and Existence of Working Examples: The specification describes lowering markers of liver fibrosis in mice, presently afflicted with liver fibrosis, by administering sotalol at concentrations between 200-1000 micromolar.
However, no working examples are given for a method of treating or inhibiting liver fibrosis in any and all subjects, with or without present liver fibrosis.
While it is noted that the applicant has shown data for relevant activity in treating liver fibrosis in mouse models by administering sotalol to mice already afflicted by liver fibrosis, the applicant is not enabled for treating or inhibiting liver fibrosis in any and all subjects, with or without liver fibrosis present.
Predictability and State of the Art: The state of the art at the time the invention was made was unpredictable and underdeveloped. It is known in the art that prevention of a disease such as liver fibrosis is undeterminable and not a guaranteed outcome.
The development of liver fibrosis is highly dependent on multiple unpredictable factors including individual genetic disposition, demographic, environmental exposures, etc.
Health. Everything You Need To Know About Liver Fibrosis, [online], [retrieved on 03/17/2026].https://www.health.com/liver-fibrosis-11688720?utm_source=copilot.com (Year:2026) - explains that there are various risk factors and genetic diseases that cause liver fibrosis, not all of which can be prevented by a single prophylactic treatment.
Amount of Experimentation Necessary: The quantity of experimentation necessary to carry out the claimed invention is high, as the skilled artisan could not rely on the prior art or instant specification to teach how to treat or inhibit liver fibrosis by administering sotalol to any and all subjects, with or without liver fibrosis present.
In order to carry out the claimed invention, one of ordinary skill in the art would have to administer sotalol as a regular, prophylactic dosing to many subjects, without liver fibrosis, over the course of a long enough period of time under conditions where it would be certain that cancer would develop, which would be an impossible experimental setup due to the duration and the lack of a true control group.
In view of the breadth of the claims and the lack of guidance provided by the specification as well as the unpredictability of the art, the skilled artisan would have required an undue amount of experimentation to make and/or use the claimed invention. Therefore, claims 11-16 are not considered to be fully enabled by the instant specification.
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.
The factual inquiries 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 11-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Deflandre, J. (The effect of sotalol on cirrhotic portal hypertension. Results of a preliminary study of cardiac and hepatic hemodynamics), Biomedicine & Pharmacotherapy, Vol. 40, no. 4, pp. 154-157 (Year: 1986).
Deflandre teaches sotalol administered intravenously at a dose of 1.5mg/kg to human subjects with liver cirrhosis, and measured a decrease in hepatic pressure.
Applicant does not define a subject (human, mouse), in need thereof (afflicted with liver fibrosis) of the method, and thus the subject of Deflandre reads on the Applicant’s claims which are construed to include all potential subjects, with or without fibrosis. Consequently, the Applicant’s claimed dose is not defined within the context of a specific subject, and thus any amount would be assumed to work within any subject.
Deflandre’s method is drawn to reduction of portal hypertension, but comprises the active steps of administration of sotalol to al subject with liver fibrosis, as patients with liver cirrhosis, such as in Deflandre’s method, inherently have liver fibrosis. Thus, as currently understood by the Examiner, Deflandre’s method would treat liver fibrosis, and effect the same fibrotic proteins in the same manner as claimed by Applicant.
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). (MPEP 2112).
Thus, as currently claimed, it would have been obvious to one having ordinary skill in the art, to develop a method of treating liver fibrosis by administering sotalol to a patient population currently afflicted with liver fibrosis.
In the instant case, Deflandre provides adequate teaching, suggestion, or motivation to administer sotalol to subjects with liver fibrosis, as they require lowering of hepatic portal hypertension. One skilled in the art would have been motivated and have had reasonable expectation of success to use the teaching of Deflandre to administer sotalol to subjects with portal hypertension to lower hepatic pressure, which would inherently treat liver fibrosis through effecting the fibrotic proteins, as claimed by the Applicant.
However, if Applicant’s claimed dosing of sotalol is critical for the claimed effect on fibrotic proteins, in subjects presently afflicted with liver fibrosis, OR
If there is a specific sub-category of subjects afflicted with liver fibrosis, such that the subjects of Deflandre would not read on the Applicant’s subject,
Examiner asks for this to be put on record.
If there is no criticality of the specific concentration of sotalol, in a specific subject population claimed by the Applicant, then any amount would be assumed to treat liver fibrosis.
In summary, Examiner requires Applicant to put on record, the full extent of requirements of the Applicant’s claims. As the claims currently read, and is currently understood by Examiner, the only requirements of the claims are any dose of sotalol to any subject, with or without current liver fibrosis.
Examiner asks: a specific subject group be defined, as well as evidence of criticality, either in the dose of sotalol or the sub-category of the subject, to be put on record.
It would have been prima facie obvious to a person having ordinary skill in the art to administer sotalol to a subject with liver fibrosis secondary to and/or concomitant with cirrhotic portal hypertension. While it is true that not all subjects with liver fibrosis have CPH, those subjects with CPH do have liver fibrosis. As such, the prior art is teaching administering the claimed API to a claimed subject population. Absent evidence to the contrary, when a claimed agent is administered to a claimed subject at a dosage of 1.5 mg/kg the results of such administration, as claimed, would naturally follow. As such, there is a reasonable and predictable expectation of success in arriving at the claimed methods in view of Deflandre.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OROD MOTEVALLI whose telephone number is (571)272-6026. The examiner can normally be reached Monday - Friday 10:00AM - 6:00PM.
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, Amy L Clark can be reached at (571) 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/OROD MOTEVALLI/ Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628