Detailed Action
► A request for continued examination under 37 CFR 1.114, including the fee set forthin 37 CFR 1.17(e), was filed on 20 AUG 2025 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Claim(s) 1, 4, 6-8, 16, 18-21, 23-27 and 29-32 is/are now pending.
► 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.
Sequence Rules
► This application complies with the sequence rules and the sequence(s) have been entered by the Scientific and Technical Information Center.
35 U.S.C. 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.
► 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.
Claim Rejection(s) under 35 U.S.C. 103
► Claim(s) 1, 4, 6-8, 16, 19-21,23-25, 27 and 29-32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tanihara [Machine translation of JP, 2002-114800 — hereinafter “¥anihara”.] in view of Tougaard et al. [Immunopharmacology and Immunotoxicity 38(1) :29-36 (2016) — hereinafter “Tougaard”], Browing, J. [Immunological Reviews (Pub. JUL 2008 – Abstract Only – hereinafter “Browning”], Angell et al [US 2009/01313167 — hereinafter Angell], Smilek et al. [Disease Models &Mechanisms 17 :503-513(2014) — hereinafter “Smilek”]; andLLehar et al. [Nature Biotechnology 27(7) :659 (2009) — hereinafter “Lehar’].
Claim 1 is drawn, in part, to a method for treating an inflammatory disease in a subject, comprising administering to the subject a therapeutically effective dose of a combination treatment of at least 3 agents to treat an inflammatory disease, the combination comprising: (1) a first agent that neutralises the receptor Tumor Necrosis Factor (TNF) receptor 1 (TNFR1); or one or more of its ligand(s) TNF or Lymphotoxin-alpha (LT-α); and (2) a second agent that neutralises one or more TRAIL receptors (TRAIL-Rs) selected from the group consisting of: TRAIL-1, TRAIL-R2, TRAIL-R3, TRAIL-R4, Osteoprotegerin (OPG) or their ligand TRAIL; and (3) a third agent that neutralises any of: (3a) the receptor CD95; or its ligand CD95L (aka FASL); (3b) the receptor Lymphotoxin beta receptor (LTβR) or one or more of its ligands Lymphotoxin-beta (LT-β ) or LIGHT; or (3c) the receptor Death Receptor 3 (DR3); or its ligand TL1A.
Yanihara teach a method for the treatment of an inflammatory disease in a subject see especially the Claims 13 and 18 which comprises therapy with a first agent which neutralises TNF mediated inflammation , a second agent which neutralizes TRAIL mediated inflammation and and a third agent which neutralizes FasL (aka CD95) mediated inflammation.
Tougaard teach the use of biologics [i.e. antagonist(s)] including a biologics targeting TNF-α (e.g. adalimumab, entracept and infliximab).
Browning teach an agent which neutralizes inflammation mediated by LTBR or one or more of its ligands.
Angell teach TRAIL antagonist and therir use in treating inflammatory disease, See at least paras 49 and 138.
Most notably, while Yanihara teach using biologics e.g. proteins having inhibitory activity against TNF mediated inflammation , a second agent which neutralizes TRAIL mediated inflammation and a third agent which inhibits FasL (aka CD95L) mediated inflammation to treat inflammatory disease (e.g. Lupus, Crohn’s disease), these inventors do not expressly teach the combined use of the three biologics recited to treat said inflammatory disease. However, combination therapies for inflammatory disease wass well known as evidenced by at least Smilek and Lehar. For example, see the section entitled “Combination therapy for autoimmune disease” bridging pps.508-509 in Smilek wherein these authors teach in part “Because a variety of non-redundant mechanism contribute to the maintenance of normal immune tolerance, the next logical step is to combine therapies to potentiate efficacy in autoimmune disease.” Smilek also teach using more than two biologics see the para bridging Columns 1-2 on p.509. Furthermore, it was known as evidenced by Lehar that “synergistc drug combination tend to improve therapeutically relevant selectivity”, see at least the title and abstract. Accordingly, absent an unexpected result it would have been prima facie obvious to the PHOSITA at the time of the invention to modify the method of Yanihara wherein the three agent described therein are used in combination as disclosed by Smilek and/or Lehar.. The PHOSITA would have been motivated to make the modification recited above in order to gain the advantages of combination therapies suggested by Smilek and/or Lehar.
► Claim(s) 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over . Yanihara_ in view of Tougaard, Browing, Angell, Smilek andLLehar as applied above against Claim 1 and further in view of Yin et al.[Agnew Chem Int Ed Engl 52(22) :5757-5761 (2013 — hereinafter “Yin”].
Claim 18 is drawn, in part, to an embodiment wherein each reagent is a single or double stranded nucleotide (e.g. siRNA). As outlined above Yanihara_ in view of Tougaard, Browing, Angell, Smilek and Lehar; reasonably suggest a method comprising most of the limitations of Claim 18 except these references fail to teach antisense therapy as required by Claim 18 (i.e. wherein each reagent is a single or double stranded nucleotide). However the use of antisense therapeutics in the treatment of inflammatory disease as required by Claim 18 was known, consider at least Fig. 1 in Yin. wherein these author teach the use of double stranded RNA (e.g. siRNA ) to neutralise TNF-a. Accordingly, absent an unexpected result it would have been prima facie obvious to the PHOSITA at the time of the invention to substitute the nucleic acid based biologic of Yin for the proteinaceous biologics of Yanihara_ in view of Tougaard, Smilek and Lehar Please note that substitution of one known second method/reagent with known properties for a first known method/reagent with known properties would have been prima facie obvious to the ordinary artisan at the time of the invention in the absence of an unexpected result. As regards the motivation to make the substitution recited above, the motivation to combine arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making this obviousness rejection comes from the M.P.E.P. at 2144.07 and 2144.09, as well as, the SCOTUS decision in KSR International. Co. v. Teleflex, Inc., et al., 550 U.S.398 (2007).
► Instant Claim 26-27 is/are rejected under 35 U.S.C. 103 as being unpatentable over . Yanihara in view Tougaard, Browing, Angell, Smilek andLLehar as applied above against Claim 1 and further in view Villa et al. [Trends in Biological Scies (OCT 1997) – “Villa “].
As regards Instant 26-27, Villa teach the use of caspase inhibitors.
Response to applicant’s Response(s)
► The applicant has traversed the outstanding rejection of Instant Claim 1, acknowledging that the prior art (e.g. Tanihara ) teach the three agents recited by Claim 1 to treat inflammatory disease. The applicant further acknowledges that while the prior art teach/suggest combination therapies to treat inflammatory disease, the prior does not expressly teach the exact combination claimed by Claim 1 as the examiner acknowledges in the 103 rejection outline above. As noted by the applicant in their Remarks, it has been hypothesized that combination therapies of the sort recited by Claim 1 might be beneficial in treating autoimmune disease. Autoimmune diseases occur when the body's immune system mistakenly attacks its own healthy tissues, leading to inflammation and tissue damage. In autoimmune diseases, inflammation is chronic and excessive. The immune system continues to attack healthy tissues, even in the absence of an infection or injury. This can lead to a variety of symptoms.
Accordingly, the prior art is replete with pharmacological regimes targeting the inflammation associated with autoimmune disease(s). See, at least for example, the following references :
Kinch, MS. An analysis of FDA-approved drugs for inflammation and autoimmune diseases.
Drug Discovery Today Col. 20,Nuber 8 pages 920-923 (2015)..
and
Li et al., Drugs for Autoimmune Inflammatory Diseases : From small molecule Compounds to Anti-TNF Biologics.
Frontiers in Pharmacology Vol . 8 Article 460 (JUL 2017)
Thus, the applicat has argued that the exact combination of biologics recited by Instant Claim 1 is not taught or suggested by the prior art. The examiner readily concedes this point, however in light of the teaching Smilek and Lehar the examiner assert that it would have been prima facie obvious, absent an unexpected results, to combine the anti-inflammatory therapies of Tanihara into a single therapeutic regime based on the teachings Smilek and Lehar who examiner assert suggest combination therapy and provide the reasonable expectation of successs necessat to sustain this rejection. It is noted that the applicant has made vague assertion(s) to the presence of unexpected result and points) to passages in the as-file specification that purport to support the finding of an unexpected result...It would appear that a more robust and detailed explanation of the asserted unexpected results is needed. The applicant is reminded that any unexpected result must be commensurate with Claim scope. See the MPEP @ 716.02(d).
Conclusion
C. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Ethan Whisenant whose telephone number is (571) 272-0754. The examiner can normally be reached Monday-Friday from 8:30 am -5:30 pm EST or any time via voice mail. If repeated attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Anne Gussow, can be reached at (571) 272-6047.
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/ETHAN C WHISENANT/Primary Examiner, Art Unit 1683 ethan.whisenant@uspto.gov
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