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 .
Response to Arguments
Applicant’s arguments, see pp. 6-8, filed 09/22/2025, with respect to the objection to claims 5 and 12; the rejection of claim 5 under 35 U.S.C. 112(b); and the rejection of claims 1-2 and 4-5 under 35 U.S.C. 102(a)(1) have been fully considered and are persuasive. Amendments moot the objection/rejections. The objection/rejections of 03/21/2025 has been withdrawn.
Applicant's arguments filed 09/22/2025 with respect to the obviousness rejection(s) have been fully considered but they are not persuasive.
Applicant’s arguments rely on the amendment to claim 1 requiring the combination of an S1R activity modulator and an IRE1 specific endonuclease inhibitor. Applicant first argues that the individual mechanisms of action of the targets, their combination would not yield expected results. Upon careful consideration, these arguments are unpersuasive for several reasons. First, the teachings of using the two components for the same purpose do not necessarily recite that the specific activities cited by applicant and their connection are solely responsible for their shared usefulness in treating inflammation. As noted by applicant on p. 11, “inflammation is a complex phenomenon mediated by several different systems not just the stress system in which IRE1 acts.” Given these complexities, applicant’s assertion that there would be “no predictable benefit” from IRE1 inhibitor treatment in the case of using an S1R agonist is not necessarily true. Additionally, the mechanistic interaction between the two targets appears to be, at least in part and based upon applicant’s recitation of the instant disclosure, a novel discovery of the inventors. Furthermore, claim 1 is not limited to S1R agonists and instead encompasses all S1R modulators, including antagonists. The alleged teaching away, while persuasive in part, is insufficient for the preponderance of the evidence to favor nonobviousness for these reasons. The teaching that targeting both S1R and IRE1 can treat inflammation remains in favor of an obviousness rejection. If applicant can show that it would be unequivocally that a PHOSITA at the time of filing would not have been motivated to combine said components, such evidence may shift the preponderance of evidence. Applicant also argues unexpected results. However, none of these results are commensurate in scope with any of the claims under examination. The results are drawn to specific gene knockout models and inhibitors, none of which have claims commensurate in scope. In summary, the alleged teachings away are not conclusive enough to overcome the obviousness of the claims and the claims are not commensurate in scope with alleged unexpected results.
Applicant notes the omission of claim 3 from the third obviousness rejection. Previous claim dependency did not require arguments regarding the use of a combination of S1R and IRE1 modulators in the treatment of septic shock; said omission did not necessarily suggest allowability of instant claim 3. Modified rejections are presented below.
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.
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 nonobviousness.
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 1-2, 5, 9-10 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Allahtavakoli et al., "Sigma-1 receptor ligand PRE-084 reduced infarct volume, neurological deficits, pro-inflammatory cytokines and enhanced anti-inflammatory cytokines after embolic stroke in rats" Brain Research Bulletin 85 (2011) 219–224 in view of Chen et al. "Inositol-Requiring Enzyme 1 Alpha Endoribonuclease Specific Inhibitor STF-083010 Alleviates Carbon Tetrachloride Induced Liver Injury and Liver Fibrosis in Mice" Front. Pharmacol., 26 November 2018.
Allahtavakoli et al. teaches that “inhibition of inflammation has been suggested for some time as a therapeutic target for stroke … inflammation contributes not only to the deleterious consequences of ischemic stroke but also to recovery and repair” (p. 219) and teaches administration of PRE-084 to rats after embolization (stroke) (Results, p. 220). Reduced pro-inflammatory cytokines and increased anti-inflammatory cytokines are observed in rats administered with PRE-084 (Fig. 4). “The ability to selectively inhibit pro-inflammatory and enhance anti-inflammatory mediators could have great potential in conditions such as stroke where there is an imbalance in the “good and bad” inflammation.” (p. 223).
Allahtavakoli et al. does not teach co-administration with an IRE1 specific endonuclease inhibitor such as STF 083010.
Chen et al. teaches that STF-083010 mitigates inflammation (p. 4). It is prima facie obvious to combine two products known for the same purpose. In the instant case, PRE-084 and STF-083010 are both taught to reduce inflammation. Therefore, it would have been obvious to administer PRE-084 and STF-083010 in combination to treat inflammation. See MPEP 2144.06(I). It would have been obvious to do so where an inflammatory response in a subject is detrimental or impaired due to the compounds’ known usefulness for treating inflammation. Allahtavakoli et al. teaches SR 31747A as a S1R modulator capable of restoring balance of pro- and anti-inflammatory cytokines. It is prima facie obvious to combine two products known for the same purpose. In the instant case, PRE-084 and SR 31747A are both taught for the purpose of treating inflammation and it would have been therefore obvious to co-administer them. See MPEP 2144.06(I).
Claims 1-3, 5, 9-10 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Allahtavakoli et al., "Sigma-1 receptor ligand PRE-084 reduced infarct volume, neurological deficits, pro-inflammatory cytokines and enhanced anti-inflammatory cytokines after embolic stroke in rats" Brain Research Bulletin 85 (2011) 219–224 in view of Chen et al. "Inositol-Requiring Enzyme 1 Alpha Endoribonuclease Specific Inhibitor STF-083010 Alleviates Carbon Tetrachloride Induced Liver Injury and Liver Fibrosis in Mice" Front. Pharmacol., 26 November 2018 in view of US 7572762 B1 to Spruce et al.
Allahtavakoli et al. teaches that “inhibition of inflammation has been suggested for some time as a therapeutic target for stroke … inflammation contributes not only to the deleterious consequences of ischemic stroke but also to recovery and repair” (p. 219) and teaches administration of PRE-084 to rats after embolization (stroke) (Results, p. 220). Reduced pro-inflammatory cytokines and increased anti-inflammatory cytokines are observed in rats administered with PRE-084 (Fig. 4). “The ability to selectively inhibit pro-inflammatory and enhance anti-inflammatory mediators could have great potential in conditions such as stroke where there is an imbalance in the “good and bad” inflammation.” (p. 223).
Allahtavakoli et al. does not teach co-administration with an IRE1 specific endonuclease inhibitor such as STF 083010 or wherein the inflammation is associated with septic shock.
Chen et al. teaches that STF-083010 mitigates inflammation (p. 4). It is prima facie obvious to combine two products known for the same purpose. In the instant case, PRE-084 and STF-083010 are both taught to reduce inflammation. Therefore, it would have been obvious to administer PRE-084 and STF-083010 in combination to treat inflammation. See MPEP 2144.06(I). It would have been obvious to do so where an inflammatory response in a subject is detrimental or impaired due to the compounds’ known usefulness for treating inflammation. Allahtavakoli et al. teaches SR 31747A as a S1R modulator capable of restoring balance of pro- and anti-inflammatory cytokines. It is prima facie obvious to combine two products known for the same purpose. In the instant case, PRE-084 and SR 31747A are both taught for the purpose of treating inflammation and it would have been therefore obvious to co-administer them. See MPEP 2144.06(I).While septic shock is not explicitly taught by Allahtavakoli et al., it strongly suggests the use of PRE-084 in the treatment of any condition involving increased/imbalanced levels of inflammation. Spruce et al. refers to “acute inflammation such as septic shock” and is generally directed toward treatment of inflammatory diseases with a S1R modulator. Accordingly, a PHOSITA would have found it obvious to utilize PRE-084, a S1R modulator which is taught by Allahtavakoli et al. to treat inflammation associated with septic shock which is taught by Spruce et al. as “acute inflammation” with a reasonable expectation of success.
Conclusion
Claims 1-3, 5, 9-10 and 12 are rejected.
Claims 6-8 and 15-26 are withdrawn.
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 JED A KUCHARCZK whose telephone number is (571)270-5206. The examiner can normally be reached Mon-Fri 7:30 to 5.
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/JED A KUCHARCZK/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623