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 .
Election/Restrictions
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Claims 6-30 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/29/2026.
Priority:
This application is a continuation-in-part of U.S. application Serial No. 17394680
filed August 5, 2021.
17394680 was abandoned after multiple rejections.
Claims of 17394680 and 18390314 are drawn to same chemical method except in the instant method the solvent is nonpolar solvent.
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.
Claims 1-5 are 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.
The scope of the term ‘nonpolar’ with respect to the solvent limitation is unclear. There is no special definition (Applicants lexicography) in the specification for what this means. Consider for example, dependent claim 3 according to which the nonpolar solvent is ethyl acetate. One of skill in the art, ethyl acetate is a carboxylic acid ester. It is a moderately polar compound containing a non-polar ethyl group, a polar carbonyl (C=O) group and a polar oxygen atom. The polarity of the carbonyl and oxygen groups that makes ethyl acetate. This is taught by Paul Sadek The HPLC Solvent Guide Wiley-Interscience, 2002.
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For this reason claim 3 lacks antecedent basis.
Dependent claims 2-5 do not solve the problem of the base claim. As such all claims 15 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.
Claim 1-5 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)). These include: (1) breadth of the claims; (2) nature of the invention; (3) state of the prior art; (4) amount of direction provided by the inventor; (5) the level of predictability in the art; (6) the existence of working examples; (7) quantity of experimentation needed to make or use the invention based on the content of the disclosure; and (8) relative skill in the art.
All of the factors have been considered with regard to the claims, with the most relevant factors discussed below.
Base claim 1:
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Disclosure with regards to the above is found at page 14 [0068], Fig.14 and at Fig.19.
Working examples for the limitation of the instant claim, for example with respect to the nonpolar solvent is not found in the pointed out disclosures, even if ethyl acetate is deemed a nonpolar solvent. Also see section under Claim Rejections - 35 USC § 112b.
Considering nature of the invention, state of the prior art and amount of direction provided in the disclosure, this Examiner has doubts on the feasibility of claimed method and enablement for reasons discussed below:
The issue here is not whether Applicant had possession of the products of formula 2, rather whether the claimed method as recited would enable one of skill in the art to make products.
Working Example:
Since there is no working example for the method, as limited by the process parameter, for example with respect to the indicated as being nonpolar solvent, the entire disclosure was taken into consideration.
The totality of the disclosure raises doubts.
Guidance and direction:
Consider Figures 14 and 16. Extending the direction/guidance in the sequence of steps in the transformations shown in these figures (that is ‘arrow pushing’) would raise doubts as to the predictable, formation of the product(s) in the claimed method.
Extending the elementary ( Clayden 2001 Organic Chemistry (1st ed.). Oxford University Press. pp. 123–133) concept of arrow pushing, for making and breaking bonds, as indicated in Fig.16 for Phe and Pro starting materials, for Figure 14 (R= COOH, that is, Trolox starting material), the compound anticipated would not be Trolox-quinone, rather a methyl ketone.
Highly reactive nature of the oxidant NaOCl coupled with the presence of multiple reactive functionalities in starting materials and products raises predictability issues as explained below.
Highly reactive nature of the oxidant NaOCl coupled with the reactive functionalities in starting material and product, raises doubts with respect to indicated exclusive formation of one product (100% yield) for reasons discussed below.
Ho, Redox Report, 5;1, 2000, 60-62 teaches the complexity of reaction of structurally similar starting materials and reagent NaOCl.
According to Ho, at page 62 column B:
The nature of the oxidant derived from NaOCI is uncertain and could be Cl2, ClOCl, H2OCl+, HOCl, ClO- or more than one of the above. Whatever the species, it may be regarded as the equivalent of Cl+ and is, almost certainly, a two electron oxidant. The mechanism for the oxidation of compound 1 in Scheme 1 reflects this fact. The first stable product of oxidation is thought to be the chlorinated chromanol (TMC-Cl), oxidation of which leads to the chlorinated quinone (TMCQ-Cl). Cyclisation of TMCQ-Cl by a Michael addition, followed by further chlorination leads to compound 1.
Oxidation of PMC is thought to proceed in exactly the same manner as that of TMC if one replaces the structure of TMC-CI in Scheme 1 by that of PMC and begins at that point.
(Note: PMC is compound in instant Figure 14, R = CH3, C1- alkyl. Note that the instant recites complex starting material more reactive R = COOH and CHO).
Although both TMC and PMC react rapidly with NaOCI at room temperature, TMC gives almost 50% more chlorinated product than does PMC and each mole of TMC uses up 3 moles of NaOCI to form the product (Scheme 1) while each mole of PMC uses up only two moles of NaOCI (Scheme 1).
As such many side reactions are anticipated for the instantly claimed method.
See also Zhou JOURNAL OF PULP AND PAPER SCIENCE: VOL. 34 NO. 4, 2008, Figures 7-9 for COOH, CHO, and alpha-hydroxy-carboxylic acid functionalities under related oxidation reaction conditions.
Unpredictable nature of organic chemical reactions is art acknowledged, for example see Dorwald, Side Reactions in Organic Synthesis, 2005, Wiley: VCH, Weinheim pg. IX of Preface pg. 1-15. At page 9, Dorwald teaches that “Even the most experienced chemist will not be able to foresee all potential pitfalls of a synthesis, specially so if multifunctional, structurally complex intermediates must be prepared. The close proximity or conformational fixation of functional groups in a large molecule can alter their reactivity to such an extent that even simple chemical transformations can no longer be performed…... Small structural variations of polyfunctional substrates might, therefore, bring about an unforeseeable change in reactivity. The instantly recited starting material and product are multifunctional (containing groups susceptible to reactions with the indicated reagent as per disclosure) compounds.
Dorwald teaching relating to reactions of radicals such as found at page 195 can be accessed by using the Control F technique on the document.
Likewise, according to Thomas, J. Am. Chem. Soc. 1989, 9, 3315-3319. See page 3318, Scheme I, the instantly speculated discrete intermediate phenoxy radical in Figure 14, for Trolox (claim 1 compound 1 R=COOH starting material), albeit generated by a different reagent undergoes many reactions other than conversion to the Trolox-Quinone claim 1 compound 2 R=COOH product). Thomas concludes, at page 3319 that phenoxy radicals from Trolox and its analogues disproportionate in aqueous solution, giving starting phenol and a product from intramolecular cyclization. The cyclization (intramolecular ‘ketalization’) product is pictured as 3 in Thomas Scheme 1. For similar conclusions on the oxidation of Trolox to Trolox-Quinone, with phenoxy radical generated by different oxidant, see Cort, Antioxidant activity and stability of 6-hydroxy-2,5,7, 8-tetramethylchroman-2- carboxylic acid. J. Am.Oil Chem. Soc., 52(6), 174-178 (1975), Figure 2, at page 116 column B; Suarna, J. Org. Chem. 1988, 53, 1281, page 1282 column B, Scheme 1; Suarna1, LIPIDS, Vol. 23, No. 12 (1988), page 1130 column B, Scheme 1.
The above cited references are not ‘out of place’ in the context of the limitations of the instant claims. The cited teachings are relevant with regards to oxidation of instantly recited starting materials wherein phenoxy radical intermediates (such as the one instant disclosure) speculated leading to unexpected products based on process parameters.
The position taken is that, in spite of all the cautionary teachings in the prior art, in the context of regards the highly reactive functional groups in the starting material & products, capricious nature of the strong oxidizing agent NaOCl the claimed method ‘may’ result some amount of the product as recited. This is not tantamount to predictable use as per 112-1 requirement.
Applicant invokes elementary arrow-pushing strategy on paper to reduce the notoriously challenging topics in organic chemistry to explain allegedly enabling complicated transformations (see below, [0059]) with spectacular results that are too good to believe.
The following from page 10 of disclosure is revealing as to the extraordinary situation faced by the Examiner:
[0059] In another aspect, the new discovery of the dual-radical character of hypochlorite in which a hydroxyl radical is involved, ushered a search for the synthesis of compounds that are typically difficult or unattainable by other methods. In that vein, E-quinone, the metabolite of a- tocopherol, one of four vitamin E, which have been successfully produced using the hydroxyl radical was evaluated with this simple method. The reaction of a-tocopherol with one equivalent of hypochlorite in an ethanol/water mixture produces 100% yield of pure red E-quinone with sodium chloride (NaCl) as the only by-product. Following the mechanism outlined before, this synthesis is detailed in FIGURE 14 where R is a C1-22 branched or linear alkyl.
Again the totality of the disclosure raises doubts. This action looks at everything the disclosure contains as a whole, for interpretation of the instant claim limitations (for example biphasic reaction medium).
The following is from the top of page 1 of the instant disclosure:
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Just as the Applicant incorporates from the disclosure of 17394680, this Examiner incorporates and invokes disclosure in office actions including interview summaries in the file wrapper of 17394680, for example (from office action filed 05/23/2024 for 17394680:
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Examination Guidelines when ‘doubt arises’:
As per MPEP 2164.03 Relationship of Predictability of the Art and the Enablement Requirement [R-07.2022]
[I]n the field of chemistry generally, there may be times when
the well-known unpredictability of chemical reactions will alone be enough to create a reasonable doubt
as to the accuracy of a particular broad statement put forward as enabling support for a claim. This will especially be the case where the statement is, on its face, contrary to generally accepted scientific principles.
And
as per MPEP 2164.04 Burden on the Examiner Under the Enablement Requirement [R-08.2017]
“it is
incumbent upon the Patent Office,
whenever a rejection on this basis is made, to explain
why it doubts the truth or accuracy
of any statement in a supporting disclosure and to back up assertions of its own with acceptable evidence or reasoning which is inconsistent with the contested statement…”
That an inorganic salt can get into an organic nonpolar medium to perform as needed for the claimed method without the use of Phase-Transfer Catalyst, Crown Ethers or Cryptands, just is not believable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIZAL S CHANDRAKUMAR whose telephone number is (571)272-6202. The examiner can normally be reached M-F 8-5 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached on (571) 272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NIZAL S CHANDRAKUMAR/Primary Examiner, Art Unit 1625
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