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 .
DETAILED ACTION
Claims 6-10, 16 and 18-20 are pending in the application. Claim 16 is rejected. Claims 6-10 and 18-20 are allowed.
Response to Amendment / Argument
Objections and rejections made in the previous Office Action that do not appear below have been overcome by Applicant's amendments to the claims. Therefore, arguments pertaining to these objections and rejections will not be addressed.
Applicant’s amendments have necessitated changes to the previously presented rejection of claim 16 under 35 USC 103; however, Applicant’s arguments will be addressed as they relate to the rejection below. On page 10 of the response filed January 13th, 2016, Applicant states the “rejection relies on generalized descriptions of reaction classes and generalized mechanistic discussions, rather than a disclosure or suggestion of the particular claimed intermediate.” The rejection is premised on a combination where the primary reference discloses particular reactants and products.
Further on page 10 of the response, Applicant states that the disclosure of Aube “is directed to a general conceptual mechanism for reaction families and to the formation of an isocyanate as the primary product, not to the identification, preparation, isolation, or possession of the specific IV-A compound having the particular polycylic scaffold and N-X substituent recited by claim 16.” The instant claims do not require isolation and Applicant does not state what would constitute possession. The Examiner’s position is that if the prior art suggests a method that would lead to an instantly claimed intermediate, the intermediate per se is unpatentable under 35 USC 103.
On pages 10 and 11, Applicant states the prior art “does not teach the claim 16 is formed under the specific conditions disclosed in Aube … nor that it would be sufficiently stable or isolable to be “a compound” that skilled artisan would have been motivated to prepare and claim.” There is no requirement that a person having ordinary skill in the art would have been motivated to isolate or claim the compound. MPEP 2143.02(II) states: “Obviousness does not require absolute predictability, but at least some degree of predictability is required. Evidence showing there was no reasonable expectation of success may support a conclusion of nonobviousness. In re Rinehart, 531 F.2d 1048, 189 USPQ 143 (CCPA 1976)”. In this situation, the prior art teaches that the reaction generally proceeds through an intermediate (that when applied to generate a product of the primary reference) would be embraced by claim 16. If Applicant is asserting that the reaction when applied to generate the compound of the primary reference would not proceed through a claimed intermediate, there is no evidence in the record to support this assertion.
On page 11 of the response, Applicant asserts the Office treats “mechanistic intermediates as automatically barring patentability for intermediate compound claims whenever a reaction class is known, is erroneous.” The Examiner’s position is that a person having ordinary skill in the art would have been familiar with common methods of generating the structures of Aube and the instant claims embrace an intermediate of one of the common methods. Applicant asserts “the question for a compound claim is whether the prior art would have taught or suggested the specific claimed structure, or a sufficiently close structural analogue, with a reason to make it and a reasonable expectation of success.” Applicant further refers to a lack of “routine substitution argument” and asserts hindsight bias for relying on Applicant’s disclosure of the specific intermediate. Applicant first appears to be demanding a “lead compound” analysis, which involves generating compounds with similar or improved properties. This is not the situation here. The motivation is to obtain an optimum method of synthesis using commonly known reactions.
On page 11 of the response, Applicant refers again to a lack of “inevitable” disclosure, which is not found persuasive for the reasons above regarding absolute predictability.
On pages 11 and 12 of the response, Applicant refers to the disclosure of Honda and its lack of disclosure of formula 16 IV-A. The disclosure of Honda demonstrates that a person having ordinary skill in the art would been able to generate the requisite materials to perform the Hofmann reaction.
For these reasons, Applicant’s arguments are not found persuasive regarding the rejection below.
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) 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over International Application Publication No. WO 2013/163344 A1 by Anderson et al. in view of Aube et al. Comprehensive Organic Synthesis II, Volume 6, 2014, pages 598-635 and in further view of U.S. Patent PGPub No. 2004/0002463 A1 by Honda et al.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Anderson et al. teach the following scheme on page 69:
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Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The prior art teaches reaction of the compound of instant formula IV by a Curtius rearrangement of an azide compound (prior art compound 1) where the instant claim 16 embraces an intermediate that would be obtained through the use of a Hofmann rearrangement.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2141.02)
Aube et al. review four related reactions (Hofmann, Curtius, Schmidt and Lossen) and state (page 598): “The title reactions of this chapter collectively convert a carbonyl-containing starting material to a nitrogenous product, either an amine or an amide, via a formal insertion process that simultaneously results in the breakage of a C–C bond.” The prior art depicts the following scheme on page 599:
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Aube et al. further compare the reactions on page 599 as follows:
The Curtius, Hofmann, and Lossen rearrangements are mechanistically and strategically related as shown in Scheme 1. Conceptually, each begins with the generation of a reactive N–X amidate or its formal equivalent. For example, the Curtius reaction, which is both the most commonly used and the oldest member of this class, entails the synthesis of an acyl azide by displacement of an acid chloride with NaN3 or, most commonly, by treatment of a carboxylic acid with diphenylphosphoryl azide (DPPA). Here, X is formally N2+, as evident in one of the two most commonly invoked resonance structures for this species. In contrast, the Hofmann and Lossen reactions each go through literal amide anions generated in situ by basic treatment of species, where X is a halogen or an acyloxy group, respectively. Once formed, these intermediates undergo rearrangement coupled with loss of the X− group (N2 in the case of the Curtius reaction) to afford an isocyanate as the primary product. […]
At least since Aube et al. teach both the Hofmann and Curtius rearrangements as two possibilities among several accomplishing the same transformation, a person having ordinary skill in the art in seeking to optimize the synthesis of Anderson et al. in terms of yield, cost, purity, safety, etc. would have been motivated to test these known methods of converting a carbonyl containing compound to an amine containing compound.
While Anderson et al. use an azide material (for a Curtius rearrangement), a person having ordinary skill in the art would have been familiar with methods that could have been used to prepare materials for a Hofmann rearrangement. For instance, Honda et al. teach the following transformations on page 9:
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Honda et al. describe the steps on page 9 (paragraph [0105]): “Dinitrile 1 was synthesized from CDDO by the method as shown in Scheme 1. Oxalyl chloride gave acyl chloride 19 in quantitative yield. Amide 3 was prepared in 91% yield from 19 with ammonia gas in benzene.” The product generated by Honda et al. could then be applied directly in the Hofmann conditions taught by Aube et al.
Aube et al. teach the use of hypervalent iodine on page 612 as follows: “Hypervalent iodine species have emerged as suitable oxidizing reagents for the Hofmann reaction; they are typically able to react with amide substrates without added base. The most common reagents in this class are organoiodine(III) compounds such as [bis
(trifluoroacetoxy)iodo]benzene 72,73–75 (diacetoxyiodo)benzene 73,76 [hydroxyl(tosyloxy)iodo]benzene 74,77 (tosylimino)phenyl-λ3-iodane 75,78 and iodosylbenzene 76 (Figure 2).79” The prior art teaches the use of both [bis(trifluoroacetoxy)iodo]benzene and (diacetoxyiodo)benzene. A person having ordinary skill in the art in seeking to optimize the choice of reagent would have at least been motivated to test the exemplary reagents taught by Aube et al.
Regarding the structure of instant claim 16, this claim embraces intermediates that would be obtained when applying [bis(trifluoroacetoxy)iodo]benzene and (diacetoxyiodo)benzene as discussed above.
Allowable Subject Matter
Claims 6-10 and 18-20 are allowed.
Conclusion
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATTHEW P COUGHLIN whose telephone number is (571)270-1311. The examiner can normally be reached Monday - Friday, 10 am - 6 pm EST.
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/MATTHEW P COUGHLIN/Primary Examiner, Art Unit 1626