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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 13, 2026, has been entered.
Response to Arguments
The examiner has withdrawn the applicability of many cited references that refer to a maximum dosage of UDCA to be 35 mg/kg and below, thereby rendering the arguments against these references moot.
The examiner relies on Cha et al. for teaching a dose of 100 mg/kg UDCA. The examiner acknowledges that Cha recites this dosage of up to 100 mg/kg but does not explicitly refer to which route of administration if acceptable for these dosages. Cha teaches intravenous administration as an acceptable route of administration. The examiner interprets the dosage range taught to be applicable to the breadth of routes of administration described. However, even if this were not the case, the instant claims include a dosage that is “about 50 mg/kg” which is interpreted to include less than 50 mg/kg. Thus, the prior art teaches an acceptable dosage to be more than twice that which is claimed and Applicant’s primary argument as to why the instant claims distinguish over the cited prior art is that the instant claims include a higher than contemplated dosage in the art. The paragraphs 56 and 60 from Cha are set forth below:
[0056] When administering the combination formulation in accordance with embodiments of the present invention, one may use the content of colchicine of 10 to 120 μg/kg, the content of the biphenyldimethyl dicarboxylate (DDB) of 5 to 30 mg/kg, the content of the silymarin of 10 to 50 mg/kg, and the content of the ursodeoxycholic acid (UDCA) of 10 to 100 mg/kg.
[0060] When the content of ursodeoxycholic acid is less than 10 mg/kg, the efficacy may not be exhibited, and when the content thereof is more than 100 mg/kg, side effects such as diabetes may occur.
Thus, not only does the prior art teach using up to 100 mg/kg, but the prior art also indicates that using above 100 mg/kg may result in a side effect. While the prior art teaches using other agents, the prior art does not indicate that UDCA would be ineffective unless administered as a combination. Moreover, the instant claims are open-ended and do not exclude unrecited limitations.
Without a showing or allegation of unexpected results, the teaching of Cha that 100 mg/kg can UDCA can be used to treat NASH, liver disease, liver cancer, and liver inflammatory conditions, in combination with other prior art references renders obvious the instant claims.
The examiner also relies on CN101028274A for teaching administration of 150 mg/kg and a slow release IV administration that can allow for less frequent administrations and presumably higher doses to be administered without substantially altering the dose that enters a subject’s system.
Overall, the administration of a dosage up to 50 mg/kg and above is obvious in view of the cited prior art. The prior art as a whole teaches treating the claimed conditions with the claimed API and provides for IV administration. While it is less common to administer above 35 mg/kg to a subject, Cha does provide this teaching. Even further, CN101028274A provides for a slow release IV administration which allows for less frequent administrations. Thus, even if a POSA would want to administer a lower dose to a subject, it is not clear that a slow release higher amount would not have an effect of a more frequent administration of a lower amount of UDCA. As such, a rejection is set forth below.
Status of the Claims
Claims 1-8 and 11-13 are pending and examined.
Claim Rejections - 35 USC § 112 (Written Description)
Claims 1-3 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. Following reasons apply:
Claims 1-3 are directed to a method of treatment by administering UDCA intravenously, although no subject populations is enumerated. This means that all subject populations are contemplated by the claim language.
The instant Specification provides a limited number of examples in which the claimed API is administered to treat a claimed subject. Gallstones and liver cancer are included in examples in the instant Specification. Moreover, the prior art teaches the claimed API as recognized for treating numerous liver conditions, e.g. Despite the support and knowledge in the art, it is not clear that Applicant contemplated the treatment of all conditions possibly treatable with the claimed agent at the claimed dosage.
The Specification does not describe other nor test nor contemplate any other specific compounds or conditions other than a specific form of liver cancer and transparent gallstone. The claimed invention is not fully described in the specification with respect to which subject populations can be treated through the claimed method. The written description requirement implements the principle that a patent must describe the technology that is sought to be patented; the requirement serves both to satisfy the inventor's obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of claimed invention.
Applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and demonstrate that by disclosure in the specification of the patent.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003).
Written description requirement, serves both to satisfy the inventor's obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed. A patentee can lawfully claim only what he has invented and described, and if he claims more his patent is void.
See MPEP 2163.01-02) for General principles governing compliance with the written description requirement applications. 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention The written description requirement has several policy objectives. “[T]he ‘essential goal’ of the description of the invention requirement is to clearly convey the information that an applicant has invented the subject matter which is claimed.” In re Barker, 559 F.2d 588, 592 n.4, 194 USPQ 470, 473 n.4 (CCPA 1977). Another objective is to convey to the public what the applicant claims as the invention. See Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1566, 43 USPQ2d 1398, 1404 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089 (1998). "The ‘written description’ requirement implements the principle that a patent must describe the technology that is sought to be patented; the requirement serves both to satisfy the inventor’s obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed." Capon v. Eshhar, 418 F.3d 1349, 1357, 76 USPQ2d 1078, 1084 (Fed. Cir. 2005). Further, the written description requirement promotes the progress of the useful arts by ensuring that patentees adequately describe their inventions in their patent specifications in exchange for the right to exclude others from practicing the invention for the duration of the patent’s term.
Genentech Inc. v. Novo Nordisk A/S (CA FC) 42 USPQ2d 1001, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion" and "patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable".
Whenever the issue of written description arises, the fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991). An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Am. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). MPEP 2163.02).
Whether the written description requirement is satisfied is a fact-based inquiry that will depend on the nature of the claimed invention and the knowledge of one skilled in the art at the time an invention is made and a patent application is filed. The written description requirement is not satisfied by the appearance of mere indistinct words in a specification or a claim, even an original claim. . A description of what a material does, rather than of what it is, usually does not suffice." Enzo, 323 F.3d at 968 (citing Eli Lilly, 119 F.3d at 1568); see Rochester, 358 F.3d at 926 ("[G]eneralized language may not suffice if it does not convey the detailed identity of an invention.").
The function of description requirement is to ensure that the inventor had possession, as of filing date of the application relied on, the specific subject matter claimed by him. See Genentech, 108 F 3d 1361, 1365 (Fed. Cir. at 1366, 78, 1999).
Written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
However, a showing of possession alone does not cure the lack of a written description. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 969-70, 63 USPQ2d 1609, 1617 (Fed. Cir. 2002). For example, it is now well accepted that a satisfactory description may be found in originally-filed claims or any other portion of the originally-filed specification. See In re Koller, 613 F.2d 819, 204 USPQ 702 (CCPA 1980); In re Gardner, 475 F.2d 1389, 177 USPQ 396 (CCPA 1973); In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). However, that does not mean that all originally-filed claims have adequate written support. The specification must still be examined to assess whether an originally-filed claim has adequate written support.
Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to that subject matter unless he can provide a description of the method and subject population sufficient to distinguish infringing methods from non-infringing methods.
It is suggested to amend the claims to represent the embodiments in the Specification that were possessed at the time of filing. More specifically, incorporate a subject to be treated that includes a condition or symptoms that are supported by the state of the art and/or the instant Specification.
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 1-8 and 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Cha, (US20210137858) (priority filing date November 13, 2019), in view of CN101028274A (cited in ISR), in view of Trauner et al., (US2009/0163459), in view of in view of Silveira et al., “Primary sclerosing cholangitis,” Can J Gastroenterol. 2008 Aug;22(8):689-98, and in view of Farrell et al., “NASH is an Inflammatory Disorder: Pathogenic, Prognostic and Therapeutic Implications,” Gut Liver, 2012 Apr;6(2):149-71.
Cha teaches compositions for treating and protecting the liver from inflammatory liver diseases comprising administration of up to 100 mg/kg UDCA. See par.’s 56 and 60. Intravenous administration is contemplated. See par. 67. UDCA was administered to improve liver function and enhance therapy of a liver condition, such as liver fibrosis. See par. 38, e.g. It provides hepatocyte protection and anti-inflammatory hepatitis agent. Non-alcoholic hepatitis is one of many inflammatory liver conditions that can be treated. See par. 17. Fatty change, fatty necrosis, and ballooning were pathological characteristic symptoms used for evaluation and showed. See Table 8.
[0056] When administering the combination formulation in accordance with embodiments of the present invention, one may use the content of colchicine of 10 to 120 μg/kg, the content of the biphenyldimethyl dicarboxylate (DDB) of 5 to 30 mg/kg, the content of the silymarin of 10 to 50 mg/kg, and the content of the ursodeoxycholic acid (UDCA) of 10 to 100 mg/kg.
[0060] When the content of ursodeoxycholic acid is less than 10 mg/kg, the efficacy may not be exhibited, and when the content thereof is more than 100 mg/kg, side effects such as diabetes may occur.
CN101028274A teaches a controlled release form of UDCA for injection to treat conditions include liver and gall diseases. See Abstract. The dosage administered includes 150 mg/kg in the UDCA injectable powder group. See Table 9. Conditions that can be treated include PBS, PSC, NASH, and others. See claim 10. The notion of a slow release would be to reduce the times needed for administration. This would appear to allow higher doses to be administered at one time while allowing for the single dose to slowly enter a subject at a rate that is consistent with more frequent administrations, such as daily or multiple day administrations, of a faster acting IV administration.
Trauner teaches UDCA “is a widely used drug to treat liver disease, wherein one of the most important indication areas of UDCA is the dissolution of gallstones and the treatment of primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC).” See par. 3. Trauner is only cited for this teaching and not used for its’ other teachings.
Silveira teaches PSC is a chronic cholestatic liver disease characterized by inflammation. See Abstract.
Farrell teaches liver inflammation has prognostic significance in NAFLD. See Abstract.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985); and Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
It would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the instant application to arrive at the claimed methods in view of Cha, CN101028274A, Trauner, Silveira, and Farrell. “One would be motivated to do so because the claimed active agent is known to treat the claimed conditions and subject populations. Further, intravenous administration is taught to be acceptable and multiple references provides preferred and non-limiting dosage amounts that overlap the claimed ranges. This include dosages taught by Cha as well as CN101028274A. Further, lower dosages can be considered equivalent to a less frequently administered higher dose that is in the form of a slower release. As such, it would be prima facie obvious to treat the claimed conditions with the claimed API, as taught, and to administer a higher dose less frequently in the form of a slower release because it would yield a same or similar and optimizable pharmacokinetic profile in a subject. Thus, there is a reasonable and predictable expectation of success in arriving at the claimed methods in view of the prior art as a whole.
As such, no claim is allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARED D BARSKY whose telephone number is (571)272-2795. The examiner can normally be reached on 9-5 M-F.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JARED BARSKY/Primary Examiner, Art Unit 1628