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 .
This is a Final Office Action.
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on May 22, 2025 is acknowledged. Group I, drawn to a method of making and/or isolating isoidide of formula (I), embraced by claims 1-9, 14, 15 and 19-22 was elected by Applicant.
Claims 1-7, 9-13, 16 and 20-22 are pending and claims 1-7, 9 and 20-22 are under examination. Claims 10-13 and 16 are withdrawn based on the restriction requirement.
Claim Objections
The objection of claim 1 because of the phrase, “selected from the group consisting of” should be removed from step M4), prior to carboxylic acid anhydrides and carboxylic acids, is withdrawn based on the amendments.
Claim Rejections - 35 USC § 112
The rejection of claim 8 under 35 U.S.C. 112, 4th paragraph, as being of improper dependent form is withdrawn based on the amendments.
The rejection of claims 14 and 15 under 35 U.S.C. 112, 4th paragraph, as being of improper dependent form is withdrawn based on the amendments.
The rejection of claim 4 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for the phrase, “the mixture of compounds of formula II provided or prepared in step M3) comprises a mixture comprising or consisting of…,” is withdrawn based on the amendments.
The rejection of claim 9 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for the phrase, “the mixture…obtained after separation in step M5) and/or one or more reaction products thereof” is withdrawn based on the amendments.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 1-5, 9 and 20-22 are rejected under AIA 35 U.S.C. 103(a) as being unpatentable over Stoss et al. (Synthesis, 1987, 174-176) in view of Matt et al. (ACS Sustainable Chemistry & Engineering, 2018, 6(12), 17382-17390).
The present application claims a process of making and/or isolating isoidide of formula (I) comprising providing or preparing a mixture of compounds of formula (II) comprising isoidide and one or both of compounds selected from isosorbide and isomannide in the presence of a metal catalyst, i.e. barium, mercury, lead and bismuth, by reacting the mixture with a carboxylic anhydride that consists of a total number of carbon atoms in the range from 2 to 8.
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The Stoss reference teaches the regioselective acylation or esterification of a mixture of 1,4:3,6-dianhydro-D-glucitol, shown in the formula scheme below using barium, mercury, lead or bismuth salts, see left-hand column under the scheme.
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The selectivity of the acylation occurs with the OH groups on the opposite face of the bridgehead hydrogens. For example, in the top part of the scheme above, compound 1 is acylated at the OH at the 5-position, which is opposite to the adjacent bridgehead hydrogen at the 4-position, in 70 to 85% yield for compounds 2a-f.
The presently claimed 90 mole % of the isolated non-esterfied isoidide is dependent on the starting composition of formula (II).
Claims 4 and 20-22 are drawn to concentrations of the different components of the M3 mixture, which is the esterified mixture or differences in temperatures for the selective esterification reaction. The reference goes on to state the yield of the acylation is affected by the R group of the anhydride, the shorter alkyl R group, shorter reaction times and decreased temperatures, favor compound 2 over compound 4, see Table 1, In other words, longer alkyl R groups, higher temperatures and longer reaction times favor the formation of compound 4. The concentration ranges are broad, e.g. 10 to 95 mole % molar ratios. The molar ratio of the nonesterified isosorbide, isomannide and isoidide to esterified, isosorbide, isomannide and isoidide, respectifully, in claim 1 will vary based on these result-effective variables.
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 105 USPQ 233, 235 (CCPA 1955). Accordingly, this type of modification would have been well within the purview of the skilled artisan and no more than an effort to optimize results.
The Stoss reference further teaches the saponification of the mixture of acylated products to obtain compounds previously difficult to make, see page 175, left-hand column.
The Stoss reference teaches a method of making and/or isolating isoidide by the separation and/or isolation of isosorbide and isomannide from a mixture of isoidide, isosorbide and isomannide, where isosorbide and isomannide are esterified, followed by a crystallization and/or distillation to isolate isosorbide and isomannide. By removing isosorbide and isomannide from the mixture, isoidide is also isolated.
Moreover, a person of ordinary skill in the art would realize the difference in properties between the esters and hydroxyl groups. Based on the changed properties obtained from the esterification or acylation versus unreacted di-ol compounds, the esterified compounds may be removed by organic solvents and the di-ols removed by water through a separating or partitioning between the two solvents. The esters would be soluble in e.g. ethyl acetate, and the di-ols in water.
The Matt reference provides this rationale with isosorbide and a single ester of isosorbide. Matt et al. teach the separation of an unreacted isosorbide and a single ester of isosorbide by way of liquid-liquid extraction, see page 17384, right-hand column, lines 1-3, that shows the separation with ethyl acetate and water.
Thus, the Stoss reference provides guidance on the separation of unreacted isoidide from the selective esterification of isomannide from isoidide.
Applicant traverses by stating, “Although the bottom route of Scheme 1 of Stoss indeed occurs for 1 hour, such a reaction is only suitable for compounds 3a-j, which include a distinct configuration of the OAc group and the OH group relative to compounds 2a-f of the top route of Scheme 1. That is, these reactions are not simply interchangeable. Rather, they require entirely different reaction conditions and produce entirely different corresponding products. It therefore would not have been obvious to a person having ordinary skill in the art to selectively choose disparate reaction conditions from Stoss to arrive at the present claims. Impermissible hindsight would have been required. Stoss is deficient at least for this reason.”
This is not persuasive. As noted in the rejection, Stoss teaches a method of making and/or isolating isoidide by the separation and/or isolation of isosorbide and isomannide from a mixture of isoidide, isosorbide and isomannide, where isosorbide and isomannide are esterified, followed by a crystallization and/or distillation to isolate isosorbide and isomannide. By removing isosorbide and isomannide from the mixture, isoidide is also isolated.
In response to Applicant's argument of improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the Applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Applicant further states, “In addition, Applicant respectfully notes that the bottom route of Scheme 1 of Stoss entirely lacks a catalyst. In contrast, the present claims recite a catalyst including barium, mercury, lead, or bismuth. That is, the bottom route of Scheme 1 of Stoss is deficient on its own. Likewise, and as previously noted, the top route of Scheme 1 of Stoss includes reaction times of 20-40 hours. The top route of Scheme 1 of Stoss is therefore also deficient on its own. Consequently, the individual reactions depicted in Stoss are deficient at least for this reason.
A person having ordinary skill in the art would necessarily have had to selectively combine the top and bottom reactions of Stoss in order to arrive at the present claims. Such a selective combination would have required at least the catalyst of the top route and the reaction time of the bottom route. However, it is unclear from Stoss whether such a reaction would have even been functional. Notably, this combination would have required decreasing the reaction time of the top route by at least 95% (i.e., a minimum of 20 hours to a maximum of 1 hour). But surely Stoss would have reported much faster reaction times if they were achievable? In any case, at most, a person having ordinary skill in the art would have had to undergo extensive experimentation to combine these reactions and assess the products. However, extensive experimentation is insufficient to establish a prima facie case of obviousness. Stoss is further deficient at least for this reason.”
This is also unpersuasive. Applicant is correct that the Stoss reference teaches two routes to selectively esterify isosorbide and provides the conditions and products obtained from both routes as shown in the scheme above. Stoss teaches the reaction to obtain compounds 2 a-f is done for 20-40 hours, but at room temperature. Stoss further states, higher temperatures afford a 2,5-diacetyl product, see page 174, first full paragraph. Therefore, one skilled in the art of organic chemistry would increase the temperature of the top route in the scheme, which would also decrease the reaction time. It is well-known in organic chemistry that an increase in temperature of a reaction, generally decreases the reaction time. Moreover, the bottom route in the scheme is only 1 hour at 120-140 ºC, see also the experimental section on page 175, right-hand column.
Applicant notes, “Moreover, Stoss is concerned with obtaining regioselectively 5- or 2-mono-acylated isosorbide. To achieve this goal, Stoss needed to accept either (1) particularly long reaction times in a metal catalyzed reaction (20-40 hours for obtaining 5-mono-acylated isosorbide, compounds 2a-f), or (2) extremely high temperatures in a non-catalyzed reaction (120-140 °C for obtaining 2- mono-acylated isosorbide, compounds 3a-j).”
This is also unpersuasive. A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). See also Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005).
Applicant further notes, “The Office acknowledged that, "The Stoss reference does not teach a method of making and/or the isolating isoidide" (see Page 8 of the Office Action dated 05/05/26).”
The rejection has been amended for clarification.
Applicant contends, “Applicant respectfully disagrees. Matt does not cure the deficiencies of Stoss at least because Matt does not teach or suggest a reaction as claimed. Rather, the cited processing of Matt occurs after synthesis with an enzyme-based catalyst. Further, similar to Stoss, the reaction of Matt likewise occurs for a period of 40 hours. Thus, Matt's reactions are outside the scope of the present claims. Matt is deficient at least for these reasons.”
This is also not persuasive. As noted in the rejection, the Matt reference is provided to show it’s known in the art how to separate unreacted isosorbide and a single ester of isosorbide by way of liquid-liquid extraction, see page 17384, right-hand column, lines 1-3, that shows the separation with ethyl acetate and water. The same method would apply to separate a diesterified isosorbide and the unreacted isosorbide.
Applicant further notes, “Further, it was found in the present application that at least anhydrides of carboxylic acids with a total number of carbon atoms <5 allow particularly efficient liquid-liquid extraction with low loss in desired yield, however, at higher cost of reagents if anhydrides of carboxylic acids with a higher total number of carbon atoms are used (see Paragraph [0278] of the published application). Indeed, it has been found in the exemplified experiments that liquid-liquid extraction as claimed is a particularly mild, convenient and efficient method of separating (by phase separation) non- esterified isoidide in high yield from a mixture comprising non-esterified isoidide and one or both compounds selected from the group consisting of esterified isosorbide and esterified isomannide, and optionally also esterified isoidide (see Paragraph [0132] of the published application). Thus, the claimed liquid-liquid extraction has unique benefits discovered in the present application.”
This is not persuasive. If there are unexpected results, Applicant should provide the data for such results in the form of an affidavit. The affidavit should provide an experimental section with details for comparison. Please be sure the declaration provides unexpected results commensurate in scope with the claims or provide sufficient data to show a trend.
MPEP 716.02(D) states, “Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of non-obviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). The non-obviousness of a broader claimed range can be supported by evidence based on unexpected results from testing a narrower range if one of ordinary skill in the art would be able to determine a trend in the exemplified data which would allow the artisan to reasonably extend the probative value thereof. In re Kollman, 595 F.2d 48, 201 USPQ 193 (CCPA 1979).
Thus, the rejection is maintained.
Claims 1-6, 9 and 20-22 are rejected under AIA 35 U.S.C. 103(a) as being unpatentable over Stoss et al. (Synthesis, 1987, 174-176) in view of Matt et al. (ACS Sustainable Chemistry & Engineering, 2018, 6(12), 17382-17390) and Le Notre et al. (ChemSusChem., 2013, 6, 693-700).
The 103 rejection above is incorporated here.
Claim 6 is drawn to a transfer hydrogenation in the presence of a transition metal catalyst to react one or more compounds selected from isosorbide, isomannide, esters of isosorbide, esters of isomannide and mixtures thereof to obtain the mixtures provided in claim 4.
Le Notre teaches the epimerization of isosorbide using ruthenium on carbon, see page 694, Scheme 1 and 2. The reference also teaches the use nickel-on-Kieselguhr, Raney nickel and ruthenium on silica as catalyst, see page 694, third full paragraph in the left-hand column.
Thus, the isomerization step in claim 6 using a transition metal is found in the Le Notre reference.
Applicant traverses by stating, “Le Notre does not the cure the deficiencies of Stoss at least because Le Notre does not teach or suggest all the elements of the present claims and has not been cited for such. Rather, the Office merely cited Le Notre for allegedly teaching the elements of claim 6. Thus, Le Notre is deficient at least for this reason.”
This is not persuasive for the same reasons noted above in the first art rejection.
Thus, the rejection is maintained.
Claims 1-7, 9 and 20-22 are rejected under AIA 35 U.S.C. 103(a) as being unpatentable over Stoss et al. (Synthesis, 1987, 174-176) in view of Matt et al. (ACS Sustainable Chemistry & Engineering, 2018, 6(12), 17382-17390), Le Notre et al. (ChemSusChem., 2013, 6, 693-700) and Dussenne et al. (Green Chemistry, 2017, 19, 5332-5344).
The 103 rejection over claims 1-6, 9 and 20-22 above is incorporated here.
Claim 7 is drawn to a method comprising reacting one or both compounds selected from the group consisting of sorbitol, mannitol and mixtures thereof, under acidic conditions, to receive one or more compounds selected from the group consisting of isosorbide, isomannide and mixtures thereof.
Dussenne et al. teach the double dehydration reaction of sorbitol to isosorbide with a variety of acids, see page 5335, Scheme 4 and page 5336, Scheme 5.
Therefore, Dussenne et al. teach the double dehydration step in claim 7 under acidic conditions.
Applicant traverses by stating, “Dussenne does not the cure the deficiencies of Stoss at least because Dussenne does not teach or suggest all the elements of the present claims and has not been cited for such. Rather, the Office merely cited Dussenne for allegedly teaching the elements of claim 7. Thus, Dussenne is deficient at least for this reason.”
This is not persuasive for the same reasons noted above in the first art rejection.
Thus, the rejection is maintained.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUSANNA MOORE whose telephone number is (571)272-9046. The examiner can normally be reached Monday - Friday, 10:00 am to 7:00 pm.
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/SUSANNA MOORE/Primary Examiner, Art Unit 1624
