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 .
Priority
This application claims the benefit of and priority US provisional application NO. 63/393,284 filed July 29, 2022, is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/06/2023 was filed prior to the mailing of the instant first Office action on the merits. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. A copy of Form PTO/SB/08 is attached to the instant Office action.
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.
Claim(s) 1-4 and 9-19 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Filep, Targeting Neutrophils for Promoting the Resolution of Inflammation, 2022, Mar16;13:866747.
Regarding claims 1-4 and 12, Filep anticipates the prevention and/or treatment of a neutrophil-related acute inflammatory condition where a subject is provided a compound of Formula 1 (as listed in the instant application). The art identifies in reference to claim 1, (Introduction, ¶1-2) where the neutrophil-driven inflammation is a common mechanism for many diseases to include reperfusion injury, arteriosclerosis, cancer, autoimmune disease, neurodegeneration and obesity. The author also mentions that an ideal therapeutic strategy would be to prevent or reverse neutrophil-mediated tissue injuries. As relevant to the instant claims, Filep discusses (p10, col 2, ¶2) whereas 4,4-dimethyl-1-(3-nitrophenyl)-2-(1H-1,2,4-triazol-1-yl)-1-penten-3-one as nexinhib20 reads to (instant claim 1) the compound structure of formula 1 (Fig 1), where R3 is a Hydrogen (instant claim 2, Fig 2), R2 is a nitro (instant claim 3) and R1 is a tert-butyl (instant claim 4) as in Fig. 3 . Finally, the reference art notes (as relevant to claim 12) that neutrophil states in healthy mice and humans can be projected onto a signal development continuum (termed neurotime) characterized by clearly defined timelines of replication (Neutrophil Heterogeneity, p.3 ¶1 as reference 63).
Formula 1 Formula 1a Nexinhib20
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Similarly, with regarding claims 13-19, Filip teaches the composition of formula 1 (p10, col 2, ¶2), where R3 is a Hydrogen, R2 is a nitro, and R3 is a tert-butyl and fully encompassed as nexinhib20 (4,4-dimethyl-1-(3-nitrophenyl)-2-(1H-1,2,4-triazol-1-yl)-1-penten-3-one) for the use within the instant claim 1.
Regarding the effects of claims 9-11, since Filip teaches administering nexhinhib20 for the prevention and/or treatment of neutrophil-related acute inflammatory condition and this is the sole required active step of the claims, this administration would necessarily result in: (i) the inhibition of neutrophil exocytosis and neutrophil adhesion; (ii) the inhibition of Interleukin 8 (IL-8) induced β2 integrin adhesion; and (iii) the suppression of intracellular calcium flux and β2 integrin activation (as in the instant claims) for the prevention and/or treatment of a neutrophil-related acute inflammatory condition.
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(s) 5-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Filep, Targeting Neutrophils for Promoting the Resolution of Inflammation, 2022, Mar16;13:866747, and further in view of Catz and McLeish, Therapeutic Targeting of Neutrophil Exocytosis, J Leukoc Biol. 2020 March ; 107(3): 393–408 .
As previously mentioned in reference to claim 1, Filip teaches a method of treatment and or prevention for (Introduction, ¶1-2) that neutrophil-driven inflammation is a common mechanism for many diseases to include reperfusion injury, arteriosclerosis, cancer, autoimmune disease, neurodegeneration and obesity. Additionally, it is mentioned where the ideal therapeutic strategy would be to prevent or reverse neutrophil-mediated tissue injuries The author further discusses (p.5, Reverse Transendothelial Migration and Lymphatic Exit, ¶1) where pathways are most prevalent in tissues subjected to ischemia-reperfusion injuries. Finally, Filep teaches (p10, col 2, ¶2) where “nexinhibs” are a potential therapeutic approach as neutrophil-specific exocytosis inhibitors with specific reference to Formula 1, where R3 is a Hydrogen, R2 is a nitro, and R3 is a tert-butyl and fully encompassed as nexinhib20 (4,4-dimethyl-1-(3-nitrophenyl)-2-(1H-1,2,4-triazol-1-yl)-1-penten-3-one) for the use within the instant claims. While Filep does teach that the interactions of neutrophils as an inflammatory response, with reference to reperfusion and ischemia-reperfusion, the art does not specifically state as myocardial ischemia-reperfusion.
Catz and McLeish teach (p9. ¶2) where neutrophil infiltration is prominent during reperfusion after ischemia of kidney, liver, myocardium and brain and where inhibition of neutrophil recruitment reduces organ injury in animal models.
Therefore, it would haven obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention for the prevention or treatment of myocardial ischemia-reperfusion when administered a compound of Formula 1 for the following reasons:
Per MPEP § 2143(I)(G), a prima facie case of obviousness exists where some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. It would have been obvious and well within the ordinary skill in the art that one would administer a compound of Formula 1 to prevent and/or the treatment of myocardial ischemia-reperfusion. The compounds of Formula 1, specifically 4,4-dimethyl-1-(3-nitrophenyl)-2-(1H-1,2,4-triazol-1-yl)-1-penten-3-one (referenced as nexhinhib20), are a neutrophil-specific exocytosis inhibitors utilized to treat conditions to include reperfusion injury, arteriosclerosis, cancer, autoimmune disease, neurodegeneration and obesity. Therefore, it would be reasonable to conclude that one would be successful in the prevention or treatment of myocardial ischemia-reperfusion with the administration of nexinhib20 because compounds of Formula 1 are neutrophil-specific exocytosis inhibitors used in the treatment of ischemia-reperfusion and the myocardium is an organ that could/would be impacted by neutrophil infiltration from ischemia as identified by Catz and Mcleish.
Summary of the Claims
Claims 1-19 are pending.
Claims 1-19 are rejected.
No claims are in condition for an allowance.
Conclusion
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/S.H.D./Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627