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 .
Response to Arguments
Applicant’s arguments, see Page 2, filed 10/03/2025, with respect to the 102 rejection of claims 1, 4-11 and 13-19 under Kabir et al. (WO 2018064472 A1) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Kabir et al. (WO 2018064472 A1) in view of Brown, Current Management of Thrombocytopenia in Chronic Liver Disease, Gastroenterol Hepatol, March 2019, Pages 155-157.
The teachings of Kabir and Brown from the previous office action is obvious to the claimed invention of a soluble solid dispersion immediate release tablet comprising about 40 mg of rifaximin twice a day.
Applicant has canceled claims 1-3 and 18-20. Claims 4-17 are now evaluated on its merits.
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, 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.
Claims 4-17 are rejected under 35 U.S.C. 103 as being unpatentable over Kabir et al. (WO 2018064472 A1) in view of Brown, Current Management of Thrombocytopenia in Chronic Liver Disease, Gastroenterol Hepatol, March 2019, Pages 155-157.
Regarding claims 4-17, Kabir teaches Kabir teaches pharmaceutical compositions as well as methods for their manufacture, and therapeutic uses associated with complications of liver disease. Of the complications Kabir teaches Overt Hepatic Encephalopathy (OHE) (as noted by Kabir rifaximin was approved by the US FDA in March 2010 for the reduction in risk of recurrent overt HE) and liver cirrhosis subjects with early decompensation by administration of a formulation comprising a therapeutically effective amount of soluble rifaximin immediate release solid dispersion (para. 0008, 0014, 0059 and 0061). The treatment as taught by Kabir reduce the time to hospitalization that is associated with complications of liver disease (e.g., liver cirrhosis complications) such as e.g., reducing and/or prevent the time to hospitalization from one or more of hepatic encephalopathy (HE), esophageal variceal bleeding (EVB), spontaneous bacterial peritonitis (SBP), and hepatorenal syndrome (HRS) (relevant to claims 5 and 8-9) (para. 0064-0065).
Kabir conducted a phase 2 study evaluating of the efficacy and safety of the composition in which rifaximin was administered in a tablet, caplet or capsule in a dosage amount of 40 mg and the subjects of the study encompassed subjects with documented ascites who had not previously experienced SBP, EVB, or HRS (relevant to claims 7 and 10) (para. 0070, 0077). The subjects were treated for 24 weeks and administered the composition once daily (para. 0077). The treatment included subjects that had Grade 1 ascites which had not developed medically refractory ascites, not previously experienced SBP and EVB, had a MELD-Na score ≥ 12 and Child-Pugh B Classification score from 7-9 (relevant to claims 6 and 13-14) (para. 0078, part 3 and 4).
Kabir teaches the efficacy endpoint of the 24-week treatment was of hospitalization associated with complications of OHE Conn score of ≥ 2 (relevant to claim 16) (para. 0081), subjects who had Conn scores less than 2 identified in Table 6 (relevant to claim 15) (para. 00102-00103, table 6) and time since subjects first diagnosis of liver cirrhosis complications or all-cause mortality observed within ≥ 947 days (relevant to claim 11) (para. 00104).
In terms of twice per day administration Kabir teaches the language “therapeutically effective amount” refers to an amount of a composition comprising a solid dispersion of rifaximin effective, upon single or multiple dose administration to the subject to provide a therapeutic benefit to the subject (para. 0016), and it should also be understood that a specific dosage and treatment regimen for any particular patient will depend upon a variety of factors, including age, body weight, general health, sex, diet, time of administration, rate of excretion, drug combination, the judgment of the treating physician, and the severity of the particular disease being treated (para. 0070).
Kabir fails to teach cirrhosis of the liver is determined by one or more histopathological evidence of cirrhosis as stated in the claim 12 limitations.
Brown teaches thrombocytopenia, defined as a platelet count under 150,000/µL, is probably the most common complication of advanced liver disease or cirrhosis. This condition tends to occur prior to the clinical manifestations associated with decompensation (ie, ascites or encephalopathy), and is often the first presenting sign of chronic liver disease (page 155, 1st para.)
Therefore, it would have been obvious to someone of ordinary skill in the art at the time of filling to have tested a patient with chronic liver disease thrombocytopenia blood platelet levels to determine if the patient has cirrhosis of the liver in order to administer rifaximin and administer rifaximin twice a day. One would have been motivated to do so from the teachings of Brown in that thrombocytopenia blood platelet levels of less than 150,000/µL determines a cirrhosis of the liver for patients with chronic liver disease and the teachings of Kabir in that a therapeutically effective amount of rifaximin refers to a single or multiple doses in which Kabir additionally teaches dosage amounts of 80 mg (para. 0070). There is a reasonable expectation of treating liver cirrhosis by testing a patient with chronic liver disease thrombocytopenia blood platelet levels to determine if the patient has cirrhosis of the liver and administrating rifaximin at 40 mg twice a day from the teachings of Kabir and Brown.
Conclusion
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 MIKHAIL O'DONNEL ROBINSON whose telephone number is (571)270-0777. The examiner can normally be reached Monday-Friday 7:30am-5:30pm.
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, Kortney Klinkel can be reached at 571-270-5239. 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.
MIKHAIL O'DONNEL. ROBINSON
Examiner
Art Unit 1627
/MIKHAIL O'DONNEL ROBINSON/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627