DETAILED ACTION
The Art Unit location of your application in the USPTO has changed. To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to Art Unit 1647. The Examiner for this Application is now Daniel C. Gamett.
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 .
Election/Restrictions
Applicant's election with traverse of Group I, claims 21-34, and of species “an inhibitor of PD1/PDL1” in the reply filed on 01/13/2026 is acknowledged. With regard to the claim groups, the traversal is on the grounds that search and examination of the four groups does not represent an undue burden on the Office. This is persuasive only insofar as Group II, claim 35, is drawn to a product that is used in the elected method of Group I. Applicant’s argument is not found persuasive with respect to Groups III and IV because those methods do not share the technical features of the treatment method or Group I or the product of Group II. Moreover, the methods of Groups III and IV are functionally distinct, they are separately classified, they would require separate searching of the prior art and they would raise separate non-prior art issues.
Therefore, the requirement for restriction between Group 1, claims 21-34 and Group II, claim 35, is hereby withdrawn. The requirement for restriction between Groups I/II, III, and IV is still deemed proper and is therefore made FINAL.
Applicant did not state a specific ground for traversal of the requirement for species election. Nevertheless, upon further consideration, the requirement for election of species set forth in the Office action mailed 11/19/2025 is hereby withdrawn.
Claim 36-40 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 01/13/2026.
Claims 21-35 are under consideration.
Claim Rejections - 35 USC § 112
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 22-24, 26, 27, and 29 are 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The phrases “e.g.” in claim 22, "such as" in claims 23, 24, 26, 27, and 29, and “preferably” in claim 23, render the respective claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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.
Claims 21, 22, 24, 25, 27, and 35 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al., Immunology Letters vol. 222:40-48, 16 March 2020 (“Chen”; of record).
Chen teaches that the expression of ATF6 is increased in liver tissues of NAFLD mice, and that the transfection of miR-149 can result in a decrease of ATF6 expression. Chen teaches that miR-149 alleviates ER stress-induced inflammation and apoptosis by down-regulating the ATF6 signaling pathway, thus inhibiting the progression of NAFLD. Chen, therefore, teaches method for treatment or prevention of a liver disease in a subject, comprising administering an inhibitor of endoplasmic reticulum (ER) stress signaling to the subject, as in claims 21, 22, 24,25, and 27. The administered miR-149 is a composition as in claim 35.
Claims 21, 26, 27, and 35 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Brada et al., Life Science 11:277-286, March 1972 (“Brada” of record). Brada (whole document) teaches a fatty liver rat model treated with 1,10-phenanthroline, a Site-2 protease inhibitor, injected subcutaneously three times per week, which significantly influences early pathological changes in liver. Brada, therefore, teaches method for treatment or prevention of a liver disease in a subject, comprising administering an inhibitor of endoplasmic reticulum (ER) stress signaling to the subject, as in claims 21, 26, and 27. The administered 1,10-phenanthroline is a composition as in claim 35.
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.
Claim 32 is rejected under 35 U.S.C. 103 as being unpatentable over Roderburg et al., Visceral Medicine 35:43-46 January 2019 (“Roderburg”; of record).
Roderburg teaches a response to anti-PD-1 therapy in a patient with hepatocellular carcinoma. Roderburg does not teach any characterization of ATF6 expression as in claim 32. However, since Roderburg teaches that treatment of liver cancer with anti-PD-1 therapy is effective, it would be obvious to treat liver cancer with anti-PD-1 therapy regardless of any knowledge of the level of ATF expression. Therefore, claim 32 is prima facie obvious in view of Roderburg.
Claims 21-35 are rejected under 35 U.S.C. 103 as being unpatentable over Chen as applied to claims 21, 22, 24, 25, 27, and 35 above, Brada as applied to claims 21, 26, 27, and 35, above, Roderburg as applied to claim 32, and further in view of Liu et al., Liver Res. 2019 Mar;3(1):55-64 (“Liu”; of record) and US 20190367497 (Alfaro).
As noted above, Chen teaches that progression of NAFLD can be inhibited by an agent that decreases ATF6 expression. Brada teaches that fatty liver can be treated by a Site-2 protease inhibitor. Roderburg establishes that checkpoint inhibitor therapy can be effective for treating hepatocellular carcinoma. These references show that particular examples of methods within the scope of the pending claims were known or obvious in the prior art before the filing of the instant application.
Liu reviews the role of the ER stress response in liver diseases. Liu teaches that NAFLD represents a spectrum of diseases associated with the accumulation of triglycerides in hepatocytes, ranging from isolated hepatic steatosis to progressive non-alcoholic steatohepatitis (NASH) that can cause progressive liver injury, fibrosis and cirrhosis. Liu teaches that ER stress induces hepatic steatosis and has been implicated in hepatocellular carcinoma. Therefore, in view of Liu, it is clear that persons of skill in the art prior to the filing of the instant application knew that ER stress is involved in all of the conditions recited for treatment in the pending claims. The particular role of ATF6 was also known. Figure 1 of Liu illustrates the translocation of ATF6 to the Golgi where it is cleaved by S1P or S2P proteases to form a fragment which is then transported to the nucleus during the ER stress response. One of skill in the art at the time of the Liu publication would interpret the effects of 1,10-phenanthroline reported in Brada as being mediated, at least in part, by inhibition of the processing and nuclear transport of ATF6, even though Brada was unaware of this mechanism of action in 1972. Therefore, in view of Liu, one skill in the art would understand that the specific examples in Brada and Chen point to a general principle that the conditions recited for treatment in the instant claims can be treated by agents that inhibit ER stress signaling, in particular ATF6 expression, stability, or translocation.
The expectation that ATF6 inhibitors should be useful for treating the recited conditions is illustrated in Alfaro. Alfaro discloses ATF6 inhibitors (Abstract) and teaches that they should be used to treat non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) [0049] and liver cancer ([0446], claim 94).
Insofar as ER stress signaling is involved in hepatocellular carcinoma (Liu) and checkpoint inhibitor therapy can be effective for treating hepatocellular carcinoma (Roderburg), it would be obvious to combine inhibition of ATF6 with checkpoint inhibitor therapy as recited in claims 30-34. It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIEL C GAMETT, Ph.D., whose telephone number is (571)272-1853. The examiner can normally be reached on M-W. Please note the examiner’s part-time schedule. 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, Joanne Hama can be reached on 5712722911. 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.
/DANIEL C GAMETT/Primary Examiner
Art Unit 1647
Prosecution Insights