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
Claims 1, 5, 10, 13-15, 17-20 are pending. Claims 2-4, 6-9, 11-12 and 16 are cancelled.
Regarding the Improper Markush rejection over claims 1-3, 5, 7, 8, 10, 12-15 and 17-20, Applicants amendments and cancellation to the claims are sufficient to overcome the rejection.
The 35 USC 112(b) rejection previously presented for claims 1-3, 5, 7, 8, 10, 12-15 and 17-20 are hereby withdrawn due to applicant’s amendments and cancellation of claims.
The 35 USC 102(a)(1) rejection over McBurney previously presented for claims 1-3, 5, 7, 8, 10, 12-15, 17 and 18 is hereby withdrawn due to applicant’s amendments to limit variables Ar1 and Ar2 to a benzotriazole moiety as depicted in claim 1.
The 35 USC 103 rejection as being unpatentable over McBurney previously presented over claims 1-3, 5, 7, 8, 10, 12-15 and 17 is hereby withdrawn due to applicant’s amendments to limit variables Ar1 and Ar2 to a benzotriazole moiety as depicted in claim 1.
Due to Applicant’s claim amendments, the following modified and new rejections are being made.
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.
Claim 1, 5, 10, 13-15, 17-20 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.
Claim 1 recites “wherein R1a is selected from L1, F, Cl,…, OC(O)N(R1a’)2, N(R1a’)C(O)N(R1a’)2, wherein R1a’ is in each cases independently….” and “wherein R1b is selected from L1, R1b’, OR1b’….OC(O)N(R1b’)2, N(R1b’)C(O)N(R1b’)2, wherein R1b’ is in each case independently….”. The substituents for R1c, R1d, Rx1a, RN, Rx2, R2a, R2b, R2c, R2d and Rx2a1 read similarly. The claims are not considered to be recited as proper Markush groupings in that at least the last two members/elements are not separated by the term “or”.
Likewise, in the last two lines of the claim read “…wherein any two or more of L1, Rx1, RN, Rx2, L2 and may together form a ring”.
The dependent claims do not resolve the issue and are also hereby rejected.
Additionally, claim 1 recites that Ar1 and Ar2 are exemplified by the formula provided in the claim.
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Given the various substituents that can be on the compound associated with Ar1 and Ar2, it is not clear where the attachment to L1 and L2 would be in the compound of the formula in claim 1.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 5, 10, 13-15, 17-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for testing NSC13378, NSC74429, and NSC25247 in in vitro screening and in animal models for cardiac arrest and cortical impact plus hemorrhagic shock, does not reasonably provide enablement for reducing organ injury resulting from an ischemic event comprising administration of a compound of the formula as shown in instant claim 1. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The instant specification fails to provide information that would allow the skilled artisan to practice the instant invention without undue experimentation. Attention is directed to In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
1. The nature of the invention and the breadth of the claims: Claim 1 is drawn to a method to reduce organ injury resulting from an ischemic event, comprising administering to a patient in need thereof a compound having the formula as shown in claim 1, with the various substituents recited within the claim, which represents an infinite number of compounds.
2. The amount of direction or guidance presented and the presence or absence of working examples: The specification includes examples utilizing compounds NSC 13378, NSC 74429, and NSC 25247, none of which read on the instant claimed compound in claim 1. The compounds are used in in vitro screening on the Staurosprine (STS) injury assay. NSC 74429 and NSC 25247 are used in in vitro screening on glutamate-excitotoxicity and hydrogen peroxide-oxidative stress assays. NSC74429 was found to inhibit pAKT473 levels in cultured primary rat cortical neurons but was not found to increase AKT473 levels in the hippocampus in vivo. NSC 74429 was found to be a neuroprotectant in adult rat asphyxia cardiac arrest and also in an adult mouse model of controlled cortical impact plus hemorrhagic shock. However, the specification does not provide any examples with a compound representing the broad compound of the formula recited in claim 1, which includes an infinite number of compounds, in reducing organ injury resulting from an ischemic event, or a model thereof.
3. The state of the prior art and the predictability or unpredictability of the art: Machara (Chemistry Select (2016), Vol. 1, pages 101-107) teaches that nitrogenous heterocyles are ubiquitous structures that exhibit a wide variety of biological activities and are used extensively in drug design. The benzotriazoles are assigned to be of 1H or 2H type which exhibit different spectroscopic, physical, chemical and biological properties. Benzotriazoles are also known to exhibit various pharmaceutical activities, including antifungal, antimycobacterial, antibacterial, anti-inflammatory, analgesic, antiviral activities, are agonists at various receptors and have inhibitory properties against various kinases (see first paragraph of Introduction for above teachings). Accordingly, the state of the art would not necessarily extrapolate the results of NSC 74429 to the entire scope of the formula of claim 1 in reducing organ injury resulting from an ischemic event.
4. The quantity of experimentation necessary: “A conclusion of lack of enablement means that, based ont eh evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/oruse the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed Cir. 1993)”. Undue experimentation would be required in order to practice Applicant’s invention because there are no examples provided in the specification as to how to reduce organ injurty resulting fron an ischemic event, comprising administration of the breadth of compounds encompassed by the formula in claim 1. One would have to determine a useful model that correlates with clinical efficacy and test compounds that encompass the breadth of compounds exemplified by the formula in claim 1, or a representative sampling, a dosage range would need to be determined as well as the most suitable route of administration. Further, if any of the above failed, then the artisan would have to start over again in an effort to determine the suitable methods, dosages ranges and routes of administration in which to determine if the breadth of the compounds will work to reduce organ injury.
Conclusion
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.
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/RENEE CLAYTOR/ Supervisory Patent Examiner, Art Unit 1691