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, filed 08/23/2023 Claims Priority from Provisional Application 63400672, filed 08/24/2022.
Status of Claims
Claims 1-20 are pending as of the response filed on 12/23/25. Applicant’s election of invention I, claims 1-17 and 20; and the species shown in the reply filed on 12/23/25 is acknowledged:
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. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). The elected species reads on claims 1-10 and 12-20 as asserted by Applicants. However, it is noted claims 18-19 read on the non-elected invention. Therefore, claims 1-10, 12-17, and 20 have been included for examination.
The elected species above has been found to be free of the prior art. Therefore, in accordance with MPEP 803.02, search and examination were extended to the following additional species: 2-fluorophenylhydrazine, which is shown in claim 14. This species has been interpreted as having X=hydrazine, L=absent; and Y=2-fluorophenyl. Therefore, claim 11 has been included for examination; in all, claims 1-17 and 20 are under examination.
Claims 18-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/23/25.
Claims 1-17 and 20 were examined and are rejected.
Claim Rejections-35 USC § 112
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 1-17 and 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 inhibiting the metalloproteins cytochrome c, Myoglobin (Mb), and DosS with a compound selected from those shown in claim 14 and Fig. 4, does not reasonably provide enablement for inhibition of any other metalloproteins with any other compounds of formula I. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. See MPEP 2164. Day et. al., J. Med. Chem., vol. 56, pp. 7997-8007, publ. 9/27/2013 is cited for discussion.
The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). The court in Wands states, “Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’” (Wands, 8 USPQ2sd 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations” (Wands, 8 USPQ2d 1404). Among these factors are: (1) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
(1) The nature of the invention and (2) the breadth of the claims:
The claims are drawn to a method to inhibit a metalloprotein comprising contacting a metalloprotein with any compound of formula I; and treating a crop comprising contacting the crop with a compound of formula I of claim 1. The scope of the claims is extensive, given the heterogeneous characteristics of metalloproteins. Additionally, formula I is defined nebulously, with X =CN, hydrazine, -SCN, -NCS, or -OCN; L is either absent or any linker, without a defined length, chemical formula, or chemical structure; and Y=any moiety that binds to a gas tunnel or a substrate tunnel of any metalloprotein.
(3) The state of the prior art and (4) the predictability or unpredictability of the art:
Metalloproteins have a wide range of characteristics and biological functions. Day teaches metalloproteins, which make up about a third of all proteins, possess diverse functions such as regulation of blood pH, matrix degradation, and DNA transcription modulation, and dysregulation of these proteins is implicated in many diseases (p. 7997, 1st para). Day further teaches given the involvement of metalloproteins in an array of biological functions, metalloprotein inhibitors have been developed and investigated for therapeutic utility, with most inhibitors being small molecules incorporating a metal binding group (MBG) (p. 7997, 2nd para). Due to the diverse nature of metalloproteins, metalloprotein inhibitors are also structurally diverse (p. 7998, Fig. 1 & Table 1). Notably, an inhibitor that shows potent activity towards one metalloprotein would not be reasonably expected to have inhibitory activity towards many other metalloproteins. For instance, while the compounds known as NSA, 1,2-HOPO-2, and CGS inhibit MMP-2 and -12, these compounds are not inhibitory towards hCAII (p. 8001, Figs. 3 & 4):
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. Additionally, the compound SAHA displayed significant inhibition towards HDAC but little or no inhibition towards MMP-2, MMP-12, and hCAII (p. 8001, Figs. 3 & 4; p. 8002, Fig. 5):
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. Thus, one of ordinary skill in the art would not have reasonably expected that any compound of formula I of the instant claims would be broadly inhibitory towards the genus of metalloproteins or metalloenzymes as claimed. Moreover, as the method of claim 20 depends on the inhibitory action of a compound of formula (I) on metalloproteins, one of ordinary skill in the art would not have had a reasonable expectation for treating or preventing any crop infection with the full scope of compounds of formula (I).
(5) The relative skill of those in the art:
The relative skill of one in the art is high, such as a person having a degree or advanced degree in chemistry or the biological sciences. Nonetheless, there is a lack of reasonable expectation of success in performing the claimed methods due to the diverse nature of metalloproteins and specificity of inhibitors for certain metalloproteins.
(6) The amount of direction or guidance presented and (7) the presence or absence of working examples:
The specification provides guidance and direction for inhibition of the metalloproteins cytochrome c, myoglobin, and M. tuberculosis DosS with the compounds shown below:
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. However, the scope of the claims is much more extensive, being drawn to inhibiting any metalloprotein with any compound of formula I. Given the high level of unpredictability in the art, and the scarcity of other evidence indicating the broad genus of compounds of formula I would have activity towards inhibiting other metalloproteins, one of ordinary skill in the art would face undue burden in practicing the full scope of the claimed methods.
(8) The quantity of experimentation necessary:
Considering the state of the art as discussed by the references above, particularly with regards to teachings of the prior art and the high unpredictability in the art as evidenced therein, and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in the scope of the claims.
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) 1-2, 11-12, and 14 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ortiz de Montellano et. al., Biochemistry, vol. 24, pp. 1147-1152, publ. 1985.
Ortiz de Montellano discloses synthesis of ortho-substituted arylhydrazine compounds, and inactivation of myoglobin with these compounds (title & abstract). In particular, Ortiz de Montellano discloses 2-fluorophenylhydrazine and contact of this compound with metmyoglobin (p. 1149, right col., last para-p. 1150, Fig. 3 and left col., para before Conclusions). Ortiz de Montellano discloses the 2-fluorophenyl moiety of the compound to be σ-bonded to the heme iron of the complex (p. 1150, 1st para of Conclusions). 2-fluorophenylhydrazine is included within formula I, having X=hydrazine, L=absent; and Y=2-fluorophenyl. Therefore, Ortiz de Montellano discloses inhibiting a metalloprotein, myoglobin, by contacting the myoglobin with a compound of formula I, 2-fluorophenylhydrazine, and anticipates the claims.
Information Disclosure Statement
The IDS filed on 8/9/24 has been considered.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH PIHONAK whose telephone number is (571)270-7710. The examiner can normally be reached Monday-Friday 9:00-5:30 EST.
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SARAH . PIHONAK
Primary Examiner
Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627