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.
The intermediate (4-X), found in claim 10, is free of the art. If the process of claim 10 is inserted into the process of claim 1, the process of claim 1 would be free of the art. Separately, incorporating by reference claim 21 into claim 1 would provide a process free of the art.
Claim Objections
Claims 10-13 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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 § 102
The rejection of claim(s) 14 is/are under 35 U.S.C. 102(a)(1) as being anticipated by Bhatt et al. (Bioorganic & Medicinal Chemistry, 2015, 23(24), 7711-7716) is withdrawn based on the amendments.
Claim Rejections - 35 USC § 102/103
The rejection of claims 15-17 under 35 U.S.C. 102(a)(1) as being anticipated by Tokumasu et al. (US 10562898), is withdrawn based on the amendments.
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.
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 1-9 are rejected under AIA 35 U.S.C. 103(a) as being unpatentable over Tokumasu et al. (US 10562898) in view of Sakaitani et al. (Journal of Organic Chemistry, 1990, 55, 870-876), and as evidenced by Hardwood et al. ((Experimental Organic Chemistry, Standard and Microscale, 2nd Edition, 1998, pp. 131-143) and Perrin et al. (Purification of Laboratory Chemicals, 3rd Edition, 1988, pp. 12-41).
The present application claims a method of producing a compound of formula (I) comprising 1) deprotecting a compound of 10-R3 to produce compound 16; and 2) without isolating compound 16 and further reacting with compound 15 to produce the compound of formula (I), as shown below:
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Tokumasu et al. teach the deprotection of 10-R3 to produce compound 16, see column 59, and column 50, where the deprotection was done with HCl. Column 35, line 41 teaches the equivalency with trifluoroacetic acid. The reference further teaches the reaction of compound 15 and 16, see column 117-118, compound A46, and see also column 81. The reference does not specifically teach “without the compound 16 isolated” in step (d-2).
According to MPEP 2144.04: In re Dilnot, 319 F.2d 188, 138 USPQ 248 (CCPA 1963) (Claim directed to a method of producing a cementitious structure wherein a stable air foam is introduced into a slurry of cementitious material differed from the prior art only in requiring the addition of the foam to be continuous. The court held the claimed continuous operation would have been obvious in light of the batch process of the prior art.). Thus, absent criticality, a continuous step in view of a batch step taught in the art is prima facie obvious.
Dependent claim 3 is drawn to the deprotection of the BOC protecting group with TMS-halogen or triflate. Sakaitani teaches the conventional deprotection of a BOC-compound (outside of the present scope) with TMS-I, Otriflate or ClO4, see page 870, reaction 4, right column.
Dependent claim 4 is drawn to specific solvents for the deprotection step. Generally, differences in solvents, concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such solvents, 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). The adjustment of particular conventional working conditions (e.g., determining result effective amounts of the solvents taught by the cited references), is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. 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.
Dependent claim 5 is drawn to the deprotection of the BOC group through a catalytic reduction, which may be accomplished with a strong acid. The Tokumasu reference teaches HCl and trifluoroacetic acid, see column 35, lines 40-41.
Dependent claims 6 and 7 are drawn to purifying the compound of formula (I) by crystallization. Purifying compounds by crystallization is a well-known and conventional organic chemistry technique, see
Crystallization or recrystallization is a commonly used technique in organic chemistry to purify solid compounds. “The simplest and most effective technique for the purification of solid organic compounds is crystallization. Crystalline compounds are easy to handle, their purity is readily assessed… and they are often easier to identify than liquids or oils. Crystals can be obtained in one of three ways: from the melted
solid on cooling, by sublimation… or from a supersaturated solution. The last method is by far the most common in the organic laboratory,” see the Crystallization paragraph on page 131 of the Hardwood reference.
Hardwood goes on to state, “The process involves five stages: dissolution.
filtration. crystallization. collection of the crystals. and drying the crystal,” see the last two lines on page 131. On page 132, the reference states, “The technique involves dissolving the impure solid in the minimum volume of a hot solvent and filtering to remove insoluble impurities. The resulting hot saturated solution of the compound, together with any soluble impurities, is set aside to cool slowly, whereupon crystals of pure compound will separate from solution,” see the bottom paragraph on page 132.
The Perrin reference teaches solvents commonly used for crystallizations, see page 14, last line, and page 40, Table 5, which teaches ethanol. The Perrin reference goes on to state, “Where a substance is too soluble in one solvent and too insoluble in another, for either to be used for recrystallisation, it is often possible (provided they are miscible) to use them as a mixed solvent. (In general, however, it is preferable to use a single solvent if this is practicable.) Table 6 comprises many of the common pairs of miscible solvents,” see page 15, first paragraph. Thus, purification of the same general approach used for single-solvent dissolution is followed when mixed solvents (solvents and anti-solvents) are employed.
The solution is allowed to cool to allow for crystal formation (crystallization will be better if this step takes place slowly). After the system reaches room temperature, cooling it in an ice bath may improve the yield. Then the solid product is isolated by filtration. The crystals normally are washed with a small amount of cold solvent during the filtration step.
The choice of solvent is perhaps the most critical step in the process of crystallization since the correct solvent must be selected to form a product of high purity and in good recovery or yield. This is considered routine optimization unless there is evidence to the contrary. 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.
Claims 8 and 9 are drawn to synthesizing compounds 10-R3 and 9-R3, see below:
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Tokumasu et al. teach both steps, see columns 59-60.
Therefore, claims 1-9 are rendered obvious.
Applicant traverses by stating, “In particular, Tokumasu et al. corresponds to W02017/135472 which is cited as Patent Literature 1 in the present specification (see page 1, line 13). Moreover, as discussed on page 11, lines 10 to 30 of the present specification, the present method is superior to the method described in Tokumasu et al. in terms of productivity.”
This is not persuasive. The mere mention of superiority is not sufficient to overcome the rejection.
Applicant further states, “Specifically, in the method of Tokumasu et al., a compound corresponding to the compound 10-R3 is deprotected by using hydrochloric acid, and the resultant solid is filtered out to obtain a hydrochloride of a compound corresponding to compound 16 (see Synthesis Example 23, columns 48 to 50 of Tokumasu et al.). The HCI salt of compound 16 is deliquescent and difficult to handle and unsuitable for mass production (see Comparative Example 1 of the present specification), whereas the present method for synthesizing the compound of Formula (1) does not go through the HCI salt of compound 16 and affords improved productivity. Furthermore, the method of Tokumasu et al. requires purification with reversed-phase HPLC in the synthesis of the compound of interest (see Example 1, columns 81 to 83 of Tokumasu et al.).”
This is also not persuasive. The claims do not exclude any additional process steps since the term “comprising” in claim 1 is open-ended. As noted in the rejection, the Tokumasu reference teaches the equivalency with trifluoroacetic acid and Sakaitani teaches the conventional deprotection of a BOC-compound (outside of the present scope) with TMS-I, Otriflate or ClO4. Moreover, claim 1 is drawn to a deprotection step in general, which does not limit the agents used for said step.
Separately, Applicant argues “unsuitable for mass production.” The claims are not limited to a process of mass production. However, the specification does not define what constitutes mass production, either.
Applicant contends, “In addition, the present claims relate to a specific process where (d-2) is performed by adding the carboxylic acid (Compound 15) and a condensing agent directly to the solution obtained in the step (d-1) without isolating the intermediate amine (Compound 16). This specific "one-pot" or continuous sequence, without forming the deliquescent HCI salt of the compound 16:
(i) avoids deliquescence problems associated with the HCI salt;
(ii) enables the compound of Formula (I) to be manufactured efficiently, leading to significant improvement of industrial productivity; and
(iii) can be carried out without purification relying on reversed-phase HPLC which is an expensive process.
Thus, the presently claimed methods provide significant process improvements for mass production, not a kind of minor modification, and provide a streamlined, high- productivity method that is remarkably advantageous over Tokumasu et al. from the viewpoint of mass production.
There is nothing in any of the secondary references which can cure the deficiencies of Tokumasu et al. Specifically, none of Sakaitani et al., Hardwood et al., and Perrin et al. contain any disclosure or suggestion of adding the carboxylic acid (Compound 15) and a condensing agent directly to the solution obtained in the step (d-1) without isolating the intermediate amine (Compound 16) or any advantages which would flow from such a process.”
This is unpersuasive based on the present claim language as noted above. Applicant is arguing a narrower claim language than what is currently presented in the claims.
Therefore, the rejection is maintained.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-9 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10562989 in view of Sakaitani et al. (Journal of Organic Chemistry, 1990, 55, 870-876), and as evidenced by Hardwood et al. ((Experimental Organic Chemistry, Standard and Microscale, 2nd Edition, 1998, pp. 131-143) and Perrin et al. (Purification of Laboratory Chemicals, 3rd Edition, 1988, pp. 12-41).
Although the conflicting claims are not identical, they are not patentably distinct from each other because the present claims are drawn to a method of making a compound of formula (I) and a general crystal compound of formula (I).
The claims in the ‘898 patent are drawn to compounds of formula (I), which embraces the present formula (I), see column 281, claim 17, first species in the ‘898 patent. Moreover, there is no patentable distinction between compounds and methods of making and the intended use of said compounds, see claims 19 and 20 in the ‘898 patent, which embrace the presently claimed utility.
The claims in the ‘898 embrace obvious variants of the presently claimed compounds also, see the second and third species in claim 17, which are either a positional isomer or a homologue. Since a methyl group is considered a homolog of hydrogen these compounds are considered equivalent. The MPEP 2144.09 states “Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).
Note also the 102 and 103 rejections above, which are incorporated herein.
Applicant states, “The rejection of Claims 1-9 and 15-17 under the judicially-created doctrine of obviousness-type double patenting in view of Claims 1-20 of U.S. Patent No. 10,562,898 (Tokumasu et al.) in view of Sakaitani et al., and as evidenced by Hardwood et al. and Perrin et al. is respectfully traversed for the same reasons set out above.”
Thus, the rejection is maintained for the same reasons set out above, which is equally applicable here.
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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/SUSANNA MOORE/Primary Examiner, Art Unit 1624
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