DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . 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 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.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/26/2024 and 05/30/2024 have been considered by the examiner.
Status of the Claims
The claims filed 05/30/2024 are under consideration.
Claims 106-125 are pending.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Rejections not reiterated herein have been withdrawn.
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
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 106-125 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 for treating hepatic cirrhosis and/or hepatic encephalopathy in a subject in need thereof, the specification does not reasonably provide enablement for preventing hepatic cirrhosis and/or hepatic encephalopathy in a subject in need thereof.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
In the May 18, 2023 decision by the Supreme Court (Court) in Amgen Inc., et al. v Sanofi et al. (Amgen Inc. v. Sanofi, 598 U.S. 594 (2023) (AMGEN)), the Supreme Court’s decision addressed whether a claim directed to a functionally defined genus complied with the enablement prong of 35 U.S.C. 112(a). The Court held that the specification must enable the full scope of the invention as defined by its claims (Amgen, e.g., pg. 13).
Here, the claimed invention is directed to methods comprising administering the claimed dosage form to subjects in need of preventing hepatic cirrhosis and/or hepatic encephalopathy.
Consistent with AMGEN, the specification must enable the full scope of methods for preventing hepatic cirrhosis and/or hepatic encephalopathy.
The specification does not provide any evidence that administering dosage forms commensurate in scope with the claimed invent are effective to prevent hepatic cirrhosis and/or hepatic encephalopathy
Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized in Ex parte Forman, 230 USPQ 546 (BPAI 1986) and reiterated by the Court of Appeals in In re Wands, 8 USPQ2nd 1400 at 1404 (CAFC 1988). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
While all of these factors are considered, a sufficient amount for a prima facie case are discussed below.
(4) Nature of the Invention: Claims 106-125 are directed to methods for preventing hepatic cirrhosis and/or hepatic encephalopathy by administering certain modified release dosage forms comprising 540-660 mg of rifamycin SV, or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients.
(2) the amount or direction presented, (3) the presence or absence of working examples
The specification offers no evidence that either cirrhosis or hepatic encephalopathy may be prevented by administering a dosage form commensurate in scope with the claimed invention.
The specification only provides description of pharmacokinetic and safety assessment of the claimed treatment, 14 days upon administration of tablets comprising 600 mg of rifamycin SV (example 4, table 7). Example 7 refers to a multicenter, randomized, double-blind placebo controlled concept of efficacy and safety of 600 mg rifamycin SV tablets. While the study is followed for 10 weeks, establishing efficacy for 10 weeks does not necessarily provide evidence for complete inhibition or prevention of either cirrhosis or hepatic encephalopathy. Thus, it appears that either cirrhosis or hepatic encephalopathy can be effectively treated, this is insufficient evidence that they can be effectively prevented.
(8) the breadth of the claims:
The recitation of preventing encompasses reducing or inhibiting the risk of acquiring or developing cirrhosis or hepatic encephalopathy, i.e., complete elimination of any risk of acquiring or developing cirrhosis or hepatic encephalopathy. See Specification, e.g., pg. 15.
Thus, the BRI of the claimed invention extends to preventing cirrhosis and/or hepatic encephalopathy by a single administration of a solid dosage form defined only as comprising 540-660 mg of rifamycin which is formulated for modified release.
The amount of guidance presented and working examples disclosed is much more limited than the invention as claimed. The specification teaches a specific dosage form (Table 1), and a specific treatment protocol for treatment. However, the claimed invention is not limited to this dosage form or specific method of treatment. Consequently, the breadth of the claimed invention exceeds the scope enabled by the specification at least because the specification does not disclose a method which is shown to achieve the prevention of cirrhosis or hepatic encephalopathy, and because the claimed method does not include the limitations of the dosage form and treatment protocol shown for efficacy in treating the claimed indications.
(5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art:
The art does not disclose an active agent or combination of active agents, recognized for prevention of the conditions cited supra. The prior art does not teach or disclose a treatment modality wherein healthy subjects are treated with rifamycin SV in order avoid the occurrence of the claimed conditions. The disclosure does not direct the skilled artisan to an art for preventing the claimed conditions.
Furthermore, the specification does not disclose required dosage forms or treatment protocols or daily doses required to prevent either cirrhosis or hepatic encephalopathy. There does not appear to be any disclosure of methods and dosage forms which naturally results in the prevention of cirrhosis or hepatic encephalopathy.
There does not appear to be any art which enables the prevention of cirrhosis with antibiotics. One skilled in the art would not be able to determine from the instant disclosure how the structure of the dosage form (such as tablet, capsule, microparticles etc.) may be changed, and which period of administration of the claimed composition of daily doses is effective to achieve a complete prevention of the occurrence of either cirrhosis or hepatic encephalopathy.
Based on the present disclosure and the knowledge offered by the prior art of record, the skilled artisan would not be able to predict which possible dosage forms within the scope of the claimed invention would be effective to prevent either cirrhosis or hepatic encephalopathy. Based on the present disclosure and the knowledge offered by the prior art of record, the skilled artisan would not be able to predict which possible daily doses and periods of administration may be required to be effective to prevent either cirrhosis or hepatic encephalopathy. The skilled artisan would be required to embark on an extensive amount of experimentation to discover the dosage forms, doses, and periods of administration required to achieve the recited goal of preventing either cirrhosis or hepatic encephalopathy.
There does not appear to be any prior art of record which bridges the gap or reduces the amount of experimentation required.
Therefore, even though the level of skill in the art is high, there is no guidance from the specification or the prior art which would allow the skilled artisan to predictably practice a method of administering a disclosed dosage form which results in complete inhibition or prevention of cirrhosis or hepatic encephalopathy within the scope of the claimed methods with a reasonable degree of certainty.
Based on the above analysis, the skilled artisan would be left to bridge the gap between the currently claimed methods and the limited guidance provided in the specification and the prior art. The
Based on the Wand’s factors analysis, it is evident that practicing methods for preventing either cirrhosis or hepatic encephalopathy over the full scope of the currently claimed methods would require undue experimentation.
Claim 108 is 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 pre-AIA the applicant regards as the invention.
Claim 108 recites “composition is formulated to release the rifamycin SV, or a pharmaceutically acceptable salt thereof, substantially in the small intestine”, which is indefinite because it is unclear what the meets and bounds of the term “substantially” are. Applicants have not provided any definition or description of the term and thus the term renders the claims indefinite.
Clarification is required.
Claim Rejections - 35 USC § 102
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 106-121 and 123-125 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Clinical Trials, "Rifamycin SV-MMX 600 mg Tablets Administered Three or Two Times Daily to Patients With IBS- D" [online], March 2017 (Search [Date August 25, 2022) <URL https /clinicaltrials.gov/ct2/history/NCT03099785'?A=1&B=1 &C=merged#StudyPageTop>, 7 pages (cited on Applicant’s IDS dated 05/30/2024) as evidenced by Di Stefano, Antimicrobial Agents and Chemotherapy, May, 2011 (cited on Applicant’s IDS dated 05/30/2024).
Copy of each reference is found in parent Application 16762760.
The study posting date appears to be March 2017. This date means the reference is available as prior art under 35 U.S.C. 102(a)(1).
The present claims recite treating and/or preventing hepatic cirrhosis and/or hepatic encephalopathy.
To the extent that the claims encompass methods for preventing hepatic cirrhosis and/or hepatic encephalopathy, it is noted that the claims encompass administering the dosage form to subjects which do not have hepatic cirrhosis or hepatic encephalopathy. The recited disease cannot be prevented unless the subject does not have the recited disease. Thus, the claimed invention is not limited to administering the claimed composition to subjects having hepatic cirrhosis and/or hepatic encephalopathy. Preventing reads on practicing the claimed method on any subject.
With that in mind, the Clinical Trials document teaches a method comprising administering a rifamycin SV-MMX 600mg tablet to subjects having IBS two or three times daily for a period of time spanning weeks. See, e.g., pg. 3/7, Arms and Interventions and Outcome Measures. This meets the limitations of claims 106 and 124-125.
This method naturally results in preventing hepatic cirrhosis and/or hepatic encephalopathy in the same way as claimed.
Tablets with a multimatrix structure (MMX tablets) have the features of claims 107, 109, 110, 117, 118, 120, 121, and 123, as evident from Di Stefano. See Di Stefano, entire document, e.g., description of rifamycin SV MMX tablets found on pg. 2123, ¶ spanning c1-c2.
Since the dosage form has the same structure as that found in claim 1, it is presumed the properties recited in claims 108, 111, 112, 113, 114, 115, 116, and 119 are inherent to the recited tablet structure disclosed in the Clinical Trial method. See MPEP 2112.01, I-II.
Clinical Trials anticipates the subject matter of claims 106-121 and 123-125.
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 of this title, 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.
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 106-110, 112-115, 117-121, and 123-125 are rejected under 35 U.S.C. 103 as being unpatentable over Forbes, US 20150141450 A1 in view of Piotrowski, Advances in Medical Sciences, 62, 2017 and Lin, US 20110171232.
The specification considers rifamycin sv and rifamycin as synonyms. See specification, e.g., ¶ spanning pp. 14-15.
Forbes teaches a method of treating subjects having hepatic encephalopathy (HE) with rifamycin class antibiotics which are gastrointestinal specific (Forbes, e.g., 0093, 0097, 0192). Subject treatment includes subjects having cirrhosis (Forbes, e.g., 0002,0053-0056, 0194, 0205, 0225-0227, 0588). Forbes claims a method for treating HE which is practiced with rifaximin specifically (Forbes, e.g., claims 1-27). Forbes teaches administering 600, 1200 or 2400 mg daily for 7 days (Forbes, e.g., 0360). Forbes teaches administering tablets comprising 550 mg of the GI specific antibiotic (Forbes, e.g., 0105 and claim 4). This amount is within the claimed range. Forbes teaches twice daily administration (Forbes, e.g., 0114, and 0138 and claim 4). Forbes teaches administration three times a day, i.e., TID (Forbes, e.g., 0649). Forbes teaches the antibiotic is effective to reduce blood ammonia concentration (Forbes, e.g., 0126). Forbes relates an increased blood ammonia level correlates to an increased risk of HE (Forbes, e.g., 0178 and 0198 and 0205 and 0226). Forbes teaches the tablets may be configured to release active ingredients in a certain portion of the gastrointestinal tract, e.g., in a delayed manner (Forbes, e.g., 0274). Forbes teaches tablets comprising an enteric coating or shell (core with a gastroresistant coating). See Forbes, e.g., 0274. Excipients within the scope of claim 109 are found in Forbes, e.g., 0272-0274, e.g., sodium citrate, starches, lactose, sucrose, mannitol, polyvinyl pyrrolidone, calcium carbonate, paraffin, magnesium stearate, gelatin, sodium starch glycolate, waxes, hydroxypropylmethylcellulose, etc.
Forbes suggests methods of treating subjects having cirrhosis and HE may be practiced with rifamycin but Forbes does not exemplify practicing the method with rifamycin.
Piotrowski teaches intestinal bacterial overgrowth is responsible for hyperammonemia which leads to hepatic encephalopathy (Piotrowski, e.g., Abstract, and pg. 348, section 5. Hepatic encephalopathy). Thus, from Piotrowski, the skilled artisan understood that treating subjects at risk for, or experiencing hepatic encephalopathy, with non-absorbable or poorly absorbable antibiotics such as rifaximin will reduce the ammonia plasma levels by eradicating intestinal bacterial overgrowth, thereby removing the hyperammonemia cause of hepatic encephalopathy.
Lin teaches bacterial overgrowth – such as SIBO associated with cirrhosis (Lin, e.g., 0047) – may be treated by at least partially eradicating the bacterial overgrowth by administering an antimicrobial agent selected from, inter alia, rifamycin or rifaximin (Lin, e.g., 0074 and claim 4). Thus, from Lin, the skilled artisan understood that rifamycin and rifaximin were both recognized in the art as effective for eliminating undesirable small intestinal bacterial overgrowth.
It would have been obvious before the effective filing date of the presently claimed invention to modify methods for treating subjects having cirrhosis and/or suffering from hepatic encephalopathy known from Forbes, by administering a tablet comprising 550 mg rifamycin modified for release in the intestines with a reasonable expectation of success. The skilled artisan would have considered this a substitution of one known antibiotic agent for another to achieve predictable results. The skilled artisan would have seen this modification as a predictable alternative solution to the problem of treating hepatic encephalopathy in subjects with antibiotic therapy. The skilled artisan would have been motivated to modify Forbes’ method of treating subjects having cirrhosis and/or suffering from HE by administering tablets containing rifamycin to subjects to eradicate small intestinal bacterial overgrowth as taught by Lin because Piotrowski teaches removing small intestinal bacterial overgrowth will remove hyperammonemia causing encephalopathy. Since Forbes teaches 550 mg rifaximin tablets are useful doses to achieve therapeutic levels which treat encephalopathy, the skilled artisan would have been motivated to administer 550 mg tablets of the alternative antibiotic rifamycin to achieve similar therapeutic levels in the gastrointestinal tract in the same way. Since the bacterial overgrowth causing hyperammonemia occurs in the small intestine, the skilled artisan would have been motivated to target release of the rifamycin tablets in the small intestine. This would have led the skilled artisan to formulate the 550 mg rifamycin tablets as enteric coated delayed release tablets targeting the small intestine. The skilled artisan would have had a reasonable expectation of success because Forbes clearly suggests rifamycin may be used to treat hepatic encephalopathy.
The combined teachings of Forbes, Piotrowski, and Lin do not expressly teach the dosage form having all the recited properties. However, since the combined teachings of Forbes, Piotrowski, and Lin teach a dosage form having all of the structural features required by claim 106, it is reasonable to conclude the skilled artisan would expect the prior art dosage form to have the properties recited in claims properties recited in claims 108, 111, 112, 113, 114, 115, 116, and 119. See MPEP 2112.01, I-II.
Accordingly, the subject matter of claims 106-110, 112-115, 117-121, and 123-125 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Claim(s) 109, 110, 111, 116, and 121-123 are rejected under 35 U.S.C. 103 as being unpatentable over Forbes, US 20150141450 A1 in view of Piotrowski, Advances in Medical Sciences, 62, 2017 and Lin, US 20110171232 as applied to claims 106-110, 112-115, 117-121, and 123-125 above, and further in view of Dutta, US 20180110800.
The combined teachings of Forbes, Piotrowski, and Lin enumerated above teach a method according to claim 106 wherein the tablet is formulated for delayed release in the small intestine, e.g., using an enteric coating. The combined teachings of Forbes, Piotrowski, and Lin do not expressly teach:
wherein the rifamycin SV, or a pharmaceutically acceptable salt thereof, is released from the solid dosage form when the solid dosage form is placed in an aqueous medium having a pH in the range of about pH 5 to about pH 6.5 (claim 111),
wherein the pharmaceutical composition releases not less than about 50% of the amount of rifamycin SV, or a pharmaceutically acceptable salt thereof, comprising the pharmaceutical composition when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 6 hours, wherein the dissolution apparatus comprises 900 mL of an aqueous buffer at pH 6.4 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm (claim 116), and
wherein the gastro-resistant coating comprises one or more of an acrylic acid polymer, an acrylic acid copolymer, a methacrylic acid polymer, and a methacrylic acid copolymer (claim 122).
Dutta teaches known techniques of configuring dosage forms for intestinal targeting include the selection of coating materials which are insoluble below about pH 5, and soluble above about pH 5 (enteric materials), e.g., having a pH threshold of 6.5-7 (Dutta, e.g., 0049). Examples of materials for intestinal targeting include gelatin, acrylate polymers, e.g., acrylate copolymers (Dutta, e.g., 0050-0052).
It would have been obvious before the effective filing date of the presently claimed invention to modify a tablet comprising 550 mg rifamycin configured for release in the small intestine administered in the method suggested by the combined teachings of Forbes, Piotrowski, and Lin by formulating the enteric coating with a polymer which releases rifamycin at a pH above 5 (enteric coating) such as pH 5.5 or 6.5 as suggested by Dutta with a reasonable expectation of success. The skilled artisan would have seen this modification as the use of known techniques to improve intestinal targeting of dosage forms to achieve the intestinal release of rifamycin as desired in the method suggested by the combined teachings of Forbes, Piotrowski, and Lin in the same way. The skilled artisan would have had a reasonable expectation of success because acrylic acid polymers and copolymers were known materials effective to achieve dissolution at the pH required to release in the small intestine.
Accordingly, the subject matter of claims 109, 110, 111, 116, and 121-123 would have been prima facie obvious before the presently claimed invention was made, absent evidence to the contrary.
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claim(s) 106-125 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 1-18 of US 12036316 alone or further in view of Forbes, US 20150141450.
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The present claims recite treating and/or preventing hepatic cirrhosis and/or hepatic encephalopathy.
To the extent that the claims encompass methods for preventing hepatic cirrhosis and/or hepatic encephalopathy, it is noted that the claims encompass administering the dosage form to subjects which do not have hepatic cirrhosis or hepatic encephalopathy. The recited disease cannot be prevented unless the subject does not have the recited disease. Thus, the claimed invention is not limited to administering the claimed composition to subjects having hepatic cirrhosis and/or hepatic encephalopathy.
With this in mind, the reference claims teach methods of treating irritable bowel syndrome (IBS) in a subject in need thereof, comprising administering to the subject an effective amount of an oral pharmaceutical composition in the form of a solid dosage form comprising 540 to 660 mg of rifamycin SV, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients; wherein the oral pharmaceutical composition is formulated to release the rifamycin SV, or a pharmaceutically acceptable salt thereof, in the small intestine, wherein the oral pharmaceutical composition further comprises at least one lipophilic compound, at least one hydrophilic compound and at least one amphiphilic compound; and a gastro-resistant coating” and, wherein the pharmaceutical composition releases not less than about 50% of the amount of rifamycin SV, oral pharmaceutically acceptable salt thereof, comprising the pharmaceutical composition when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 6 hours, wherein the dissolution apparatus comprises 900 mL of an aqueous buffer at pH 6.4 and at a temperature of 37+0.5° C., and wherein the aqueous solution is stirred at a rate of 100 rpm. The claimed doses are found in reference claims 4-6. The limitations of claims 112-115 are found in reference claims 12-15. The limitations of claims 117 and 119 are found in reference claims 16-17. The reference claims are silent to ethanol.
Since the reference claims teach administering a tablet within the scope of the claimed invention to a subject, the reference claims anticipate the claimed invention to the extent that preventing means the claimed invention is not limited to administering the claimed composition to subjects having hepatic cirrhosis and/or hepatic encephalopathy. That is, practicing the method of the reference claims will naturally result in preventing hepatic cirrhosis and/or hepatic encephalopathy as claimed.
For treating subjects having hepatic cirrhosis and/or hepatic encephalopathy:
The reference claims do not expressly teach treating hepatic cirrhosis and/or hepatic encephalopathy.
Forbes teaches rifamycin class antibiotics were known and used to treat subjects having (HE) hepatic encephalopathy (Forbes, e.g., 0093, 0097) and subjects having liver cirrhosis and HE (Forbes, e.g., 0053-0056, 0194, and 0205). Forbes names rifamycin as a rifamycin class antibiotic (Forbes, e.g., 0192). Forbes teaches subjects having IBS or diarrhea which also suffer from hepatic insufficiency (Forbes, e.g., 0204-205).
It would have been obvious before the effective filing date of the presently claimed invention to administer a dosage form containing rifamycin sv as claimed by the reference patent to subjects suffering from hepatic cirrhosis and/or hepatic encephalopathy with a reasonable expectation of success. Since the reference claims teach administering the dosage forms to subjects having IBS and since Forbes teaches treating subjects having IBS with rifamycin class antibiotics who also suffer from hepatic insufficiency, e.g., cirrhosis and/or hepatic encephalopathy, the skilled artisan would have been motivated to practice methods claimed by the reference application on subjects suffering from cirrhosis and/or hepatic encephalopathy with a reasonable expectation of success. Subjects suffering from cirrhosis and/or hepatic encephalopathy were a known, and art recognized, subset of patients having irritable bowel syndrome in need of treatment with rifamycin class antibiotics. The skilled artisan would have had a reasonable expectation of success since Forbes suggests treatment may be affected with rifamycin which is rifamycin sv.
Accordingly, the subject matter of claims 106-125 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Claim(s) 106-125 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 1-18 of US 11564883 in view of Forbes, US 20150141450.
The present claims recite treating and/or preventing hepatic cirrhosis and/or hepatic encephalopathy.
To the extent that the claims encompass methods for preventing hepatic cirrhosis and/or hepatic encephalopathy, it is noted that the claims encompass administering the dosage form to subjects which do not have hepatic cirrhosis or hepatic encephalopathy. The recited disease cannot be prevented unless the subject does not have the recited disease. Thus, the claimed invention is not limited to administering the claimed composition to subjects having hepatic cirrhosis and/or hepatic encephalopathy.
With this in mind, the reference claims teach an oral pharmaceutical composition in the form of a solid dosage form comprising 540-660 mg of rifamycin SV, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients,
wherein the oral pharmaceutical composition further comprises:
(a) one or more lipophilic compounds selected from the group consisting of (i) unsaturated or hydrogenated alcohol, (ii) fatty acid, salt, or ester thereof, (iii) fatty acid mono-, di- or triglyceride or polyethoxylated derivative thereof, (iv) wax, (v)ceramide, (vi) cholesterol derivative or mixture thereof, (b) one or more hydrophilic compounds, and (c) one or more amphiphilic compound; and a gastro-resistant coating comprising a polymer selected from the group consisting of methacrylic acid-methyl methacrylate copolymer 1:2, methacrylic acid methyl methacrylate 1:1 copolymer, and methylacrylic acid-ethylacrylate 1:1 copolymer, and
wherein the pharmaceutical composition is formulated for modified release,
wherein the solid dosage form comprises a core and the gastro-resistant coating covering the core,
wherein the pharmaceutical composition releases not less than about 50% of the amount of rifamycin SV, or a pharmaceutically acceptable salt thereof, comprising the pharmaceutical composition when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 6 hours, wherein the dissolution apparatus comprises 900 mL of an aqueous buffer at pH 6.4 and at a temperature of 37±0.5° C., and wherein the aqueous solution is stirred at a rate of 100 rpm, and
wherein the oral pharmaceutical composition releases the rifamycin SV, or a pharmaceutically acceptable salt thereof, when the solid dosage form is placed in an aqueous medium having a pH in the range of about pH 5 to about pH 6.5. Limitations of claims 112-115 are found in reference claims 3-6. Limitations of claims 117-119 are found in reference claims 8-11. The limitations of claims 124-125 are found in reference claim 15.
The reference claims teach treating subjects with the dosage form, e.g., for small intestine bacterial overgrowth (SIBO), irritable bowel syndrome (IBS), IBS having predominant diarrhea (IBS-D), IBS having alternated predominant diarrhea or constipation (IBS-M), or cholera (reference claims 14-16).
Since the reference claims teach administering a tablet within the scope of the claimed invention to a subject, the reference claims anticipate the claimed invention to the extent that preventing means the claimed invention is not limited to administering the claimed composition to subjects having hepatic cirrhosis and/or hepatic encephalopathy. That is, practicing the method of the reference claims will naturally result in preventing hepatic cirrhosis and/or hepatic encephalopathy as claimed.
For treating subjects having hepatic cirrhosis and/or hepatic encephalopathy:
The reference claims do not expressly teach treating hepatic cirrhosis and/or hepatic encephalopathy.
Forbes teaches rifamycin class antibiotics were known and used to treat subjects having (HE) hepatic encephalopathy (Forbes, e.g., 0093, 0097) and subjects having liver cirrhosis and HE (Forbes, e.g., 0053-0056, 0194, and 0205). Forbes names rifamycin as a rifamycin class antibiotic (Forbes, e.g., 0192). Forbes teaches subjects having IBS or diarrhea which also suffer from hepatic insufficiency (Forbes, e.g., 0204-205).
It would have been obvious before the effective filing date of the presently claimed invention to administer a dosage form containing rifamycin sv as claimed by the reference patent to subjects suffering from hepatic cirrhosis and/or hepatic encephalopathy with a reasonable expectation of success. Since the reference claims teach administering the dosage forms to subjects having IBS and since Forbes teaches treating subjects having IBS with rifamycin class antibiotics who also suffer from hepatic insufficiency, e.g., cirrhosis and/or hepatic encephalopathy, the skilled artisan would have been motivated to practice methods claimed by the reference application on subjects suffering from cirrhosis and/or hepatic encephalopathy with a reasonable expectation of success. Subjects suffering from cirrhosis and/or hepatic encephalopathy were a known, and art recognized, subset of patients having irritable bowel syndrome in need of treatment with rifamycin class antibiotics. The skilled artisan would have had a reasonable expectation of success since Forbes suggests treatment may be affected with rifamycin which is rifamycin sv.
Accordingly, the subject matter of claims 106-125 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM A CRAIGO whose telephone number is (571)270-1347. The examiner can normally be reached on Monday - Friday, 9am - 6pm, PDT.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A WAX can be reached on 571-272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM CRAIGO/Examiner, Art Unit 1615