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 .
Claim status
Claims 1-20 are pending and have been examined on the merits.
Withdrawn Rejections
The rejection of claims 1-10 and 20 are rejected under 35 U.S.C. 112(b) is withdrawn due to the Applicant’s persuasive argument.
Maintained Rejections
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3 and 5-9 are rejected under 35 U.S.C. 102(a)(l) as being anticipated by Pruzanski et al. (WO2016127019).
Regarding claims 1 and 9, Pruzanski ‘019 anticipates the claims by teaching (abstract and page 4, line 1-3, 13 and 14, page 14, line 27-30) “a pharmaceutical composition comprising (i) a first compound, (ii) at least one fibrate, (iii) at least one statin, and optionally (iv) one or more pharmaceutically acceptable carriers, wherein the first compound is an FXR agonist.” The treatment is comprising administering a therapeutically effective amount of a pharmaceutical composition to a subject in need thereof. The composition is to treat or prevent, but not limited to, liver diseases (including cholestatic and non-cholestatic liver diseases) such as primary biliary cirrhosis (PBC), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). While Pruzanski does not explicitly use the phrase “ameliorating”; given that Pruzanski discloses a method of treating or preventing, then by definition, the method is intended to ameliorate the condition.
Therefore, claim 1 and 9 are anticipated.
Regarding claim 3, Pruzanski (page 10) teach the same compound that meet each and every chemical structure variable of formula A:
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Therefore, claims 3 is anticipated.
Regarding claim 5, Pruzanski (page 10) teaches the same compound that meet each and every chemical structure variable of formula A
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Therefore, claims 5 is anticipated.
Regarding claim 6, Pruzanski (page 10) teaches compounds that meets each and every chemical structure variable of formula A is Compound 3a or Compound 3b:
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Therefore, claims 6 is anticipated.
Regarding 7, Pruzanski (page 11, line 15-16) teaches the first compound is any FXR agonist or obeticholic acid.
Therefore, claims 7 is anticipated.
Regarding 8, Pruzanski (page 11, line 19-21) teaches that the fibrate is selected from the group consisting of fenofibrate, bezafibrate.
Therefore, claims 8 is anticipated.
Regarding 9, Pruzanski (page 16, line 17-18) teaches a cholestatic condition is selected from the group consisting of primary biliary and cirrhosis (PBC), as an example. PBC and primary biliary cholangitis are the same disease condition.
Therefore, claims 9 is anticipated.
Claims 2 and 4 are rejected under 35 U.S.C. 102(a)(l) as being anticipated by Pellicciari et al. (WO2014184271).
Regarding claims 2 and 4, Pellicciari (page 10) teaches a compound 100, FXR agonists, that meets each and every chemical structure variable, wherein R1, R2 and R5 are OH; R3 and R6,
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R8, R9, R12, R11 are H; R4 is ethyl (alkyl); m =1, and n = 1; p is 0; R7 is COOH.
Therefore, claims 2 and 4 are anticipated.
Maintained Rejections
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office
action.
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
Non-obviousness.
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.
Claims 10-19 are rejected under 35 U.S.C. 103 as being unpatentable over Pruzanski and Pellicciari, as applied to claims 1-9 above, in further view of Smets et al. (Journal of Hepatology, 70(1), e130), and Everson, G. T. (2018). (https://cdn.clinicaltrials.gov/large docs/41/NCT03294941/Prot_SAP_000.pdf).
The claims and teachings of Pruzanski are as of record.
Regarding claims 10-16, the combined teachings Pruzanski and Pellicciari disclose a pharmaceutical composition comprising an FXR agonist and a fibrate, to treat or prevent cholestatic disease.
Regarding claim 10-16, Pruzanski (page 21, lines 8-11) teaches
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Pruzanski (page 62, lines 12-13) discloses
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Pruzanski (page 40, lines 8-11; page 23 bridged page 24) teaches the following regarding OCA dosing
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Pruzanski (page 28 bridged page 29) teaches the following regarding bezafibrate dosing
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Pruzanski (page 24, line 29 bridged page 25) teaches the composition can be administered in single daily doses, or in two, three, four or more identical or different divided doses per day, and
they may be administered simultaneously or at different times during the day. This is supported by Smets (page 1, left col.), however, teaches a pharmaceutical composition comprising OCA (5 or 10 mg/daily) and bezafibrate (Eulitop 400 mg/daily) to treat primary biliary cholangitis (PBC). Therefore, it would have been obvious with a reasonable expectation of success to POSITA at the time of filling of the instant application to combine the teachings Pruzanski and Pellicciari in view of Smets to arrive at the claimed invention, because Pruzanski clearly teaches the use of OCA and bezafibrate to treat a patient with PBC.
Regarding claim 17-19, the combined teachings Pruzanski and Pellicciari does not explicitly teach assessing, monitoring, measuring, or detecting liver function.
Smets (page 1, left col.) teaches measurement for liver function (ALP (U/L), BILI (μMOL/L), AST (U/L), ALT (U/L), and GGT (U/L). These tests are commonly used in the art to assess liver function. Thus, it is reasonable to infer that Smets discloses standard methods or step of assessing, monitoring, measuring, or detecting liver function in patients with liver disease or PBC.
Smets, however, does not explicitly mention HepQuant SHUNT, a non-invasive assay.
Everson (page 10) teaches “HepQuant SHUNT test to monitor liver disease and treatment effects by measuring liver function and physiology.” Thus, a POSITA is likely to recommend HepQuant SHUNT as a method to monitor treatment and liver disease progression. Therefore, it would have been obvious to a POSITA with reasonable expectation of success to modify Pruzanski’s teachings in view of Everson and Smet regarding measurement for liver function, to arrive at the claimed invention, because liver function assessment plays a crucial role in evaluating the effectiveness of liver treatments and managing liver diseases.
Claims 20 is rejected under 35 U.S.C. 103 as being unpatentable over Pruzanski, Pellicciari, Smets, Everson, as applied to claims 1-19 above, in further view of Hirschfield et al. (2014). (Gastroenterology), 148(4), 751-761.e8.
Pruzanski/Pellicciari/Smets/Everson teach a pharmaceutical composition comprising an FXR agonist and a fibrate, to treat or prevent cholestatic. Pruzanski (page 10, lines 19-20) acknowledges that certain drugs are ineffective for patients who have developed drug resistance to, e.g., ursodeoxycholic acid. However, Pruzanski does not explicitly indicate to treat such patients with FXR agonist and fibrate pharmaceutical composition.
Hirschfield (page 759, right col.), however, teaches “randomized controlled clinical
trial data demonstrating biochemical efficacy of OCA, a FXR agonist, when given to patients with PBC with an inadequate response to (ursodeoxycholic acid) UDCA therapy.” Given that UDCA appears to be and ineffective treatment, thus a POSITA would likely recommend an alternative treatment approach, such as a combination of an FXR agonist and a fibrate.
From the teachings of the references, it is apparent that a POSITA would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Rejection under 35 U.S.C. §102/103
Applicant argues that Pruzanski or Pellicciari, Smets, Everson or Hirschfield fails to disclose ameliorating a cholestatic liver disease, Applicant accordingly respectfully requests reconsideration and withdrawal of the rejection. Applicant’s argument is not persuasive because in clinical setting or practice, the measurement of treatment outcomes routinely includes not only the cure or prevention of the disease but also any amelioration of the overall condition. Thus, the fact that Pruzanski, as an example, teaches a method of treating or preventing PBC, thus a POSITA would understand that amelioration of the disease, whether symptoms reduction or disease progression, is also encompassed within the scope of the treatment. Therefore, Prozanski’s disclosure of treatment inherently indicates ameliorative effects as a routine and expected results.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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.
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/P.P.E./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622