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 .
CONTINUING DATA
This application is a 371 of PCT/EP2020/086385 12/16/2020
FOREIGN APPLICATIONS
EP 19216405.1 12/16/2019
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on May 15, 2026 has been entered.
Claims 37-41 and 43-56 are pending.
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.
Claim 38 is 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.
Claim 38 recites “with 5-ethynyl-1,2,3-trifluuorobenzene,” but does not recite what is happening with 5-ethynyl-1,2,3-trifluuorobenzene. The recitation “reacting a compound of formula IX” was removed from the claim, so it is unclear what the claim actually requires.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 37-41, 43-46, and 52-56 is/are rejected under 35 U.S.C. 103 as being unpatentable over Brimert in view of Kay (Factors that Affect the Rate of Reactions, in Chapter 17 of Introductory Chemistry – 1st Canadian Edition, 2014).
Brimert teaches a process where the following compound (1.29 mmol)
PNG
media_image1.png
180
224
media_image1.png
Greyscale
was reacted in 15 mL DMF (a polar aprotic solvent) with trimethyl-[2-(3,4,5-trifluorophenyl)ethynyl]silane (1.94 mmol*), iodocopper (0.39 mmol), CsF, and N,N-diethanamine. The vessel was purged 3 times with nitrogen (inert atmosphere). The reaction mixture was stirred at room temperature for 2 hours. This starting material is a compound of formula IX where each of R1, R2, and R3 are acetyl. See pages 146-148.
The resulting compound is a compound of formula X where each of R1, R2, and R3 are acetyl.
PNG
media_image2.png
188
373
media_image2.png
Greyscale
Then the protected compound was dissolved in methanol followed by addition of sodium methoxide and the mixture was stirred at room temperature for 1 hour to give the following compound, which is claimed formula I. The product was washed with methanol and concentrated in vacuo. Page 136.
PNG
media_image3.png
178
285
media_image3.png
Greyscale
Brimert also teaches the reaction where 5-bromopyridine-3-thiol is reacted with NaH (base) in DMF at room temperature for 30 minutes. Then 2,4,6-tri-O-acetyl-3-azido-1-chloro-3-deoxy-beta-D-galactopyranoside was added and the reaction mixture was stirred at 50°C for two hours. The starting compound was a compound of formula IX where R1, R2 and R3 are all acetyl (protecting groups).
PNG
media_image4.png
199
230
media_image4.png
Greyscale
*Brimert recites that trimethyl-[2-(3,4,5-trifluorophenyl)ethynyl]silane was present at 194 mmol, which is clearly a typographical error. The molecular weight of the compound is 228.28 g/mol and the amount used was 442.22 mg, which is 1.94 mmol.
Brimert also teaches reactions corresponding to claimed step (a) with different substrates (different rings attached to S). On page 204, the reaction was heated to 100oC for two hours after adding the base. One page 201-202, the reaction was heated to 50oC for 1 hour after adding the base. On page 220, the reaction was heated to 100oC for two hours after adding the base. One page 221, the reaction was heated to 100oC for 30 minutes after adding the base. These are only a few examples of reactions which were heated in the step corresponding to claimed step (a).
In Brimert’s example illustrated above, the reaction mixture in step (a) is not heated to temperature at least 15°C above the suitable temperature.
Kay teaches that an increase in temperature increases the rate of reaction.
It would have been obvious to one of ordinary skill in the art at the time the application was filed to increase the temperature of the Brimert reaction in order to increase the rate of reaction. MPEP 2144 states ‘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. “[W]here 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.”’ The skilled artisan would have increased the temperature in order to increase the rate of reaction, and would have optimized the temperature using routine experimentation to provide an acceptable rate of reaction versus formation of side products. The skilled artisan would have optimized the temperature using the guidance provided by Brimert for analogous reactions.
Claim(s) 47 is/are rejected under 35 U.S.C. 103 as being unpatentable over Brimert in view of Kay.
Brimert teaches as set forth above, the use of diethanamine for step b. Diethanamine is not a tertiary amine base. Kay teaches as set forth above.
Brimert also teaches the same reaction for production of a compound which differs from (I) only because it contains F instead of Br attached to phenyl. Page 124. The base used in that example was triethylamine.
PNG
media_image5.png
194
310
media_image5.png
Greyscale
It would have been obvious to one of ordinary skill in the art at the time the application was filed to substitute triethylamine for diethanamine in Brimert’s reaction because both are amine bases used in the same reaction for substrates which differ only in a choice of halogen. The Supreme Court in KSR reaffirmed the familiar framework for determining obviousness as set forth in Graham v. John Deere Co. (383 U.S. 1, 148 USPQ 459 (1966)), but stated that the Federal Circuit had erred by applying the teaching- suggestion-motivation (TSM) test in an overly rigid and formalistic way. KSR, 82 USPQ2d 1385. Exemplary rationales that may support a conclusion of obviousness include simple substitution of one known element for another to obtain predictable results. Simple substitution of triethylamine for diethanamine would have resulted in the claimed invention, and the results would have been predictable because triethylamine has been used to carry out the same reaction on a compound which differs only in the choice of halogen at a position which was not the reaction site. The skilled artisan would have optimized the temperature of the reaction using routine experimentation to provide an acceptable rate of reaction versus formation of side products, as set forth above.
Claim(s) 48-51 is/are rejected under 35 U.S.C. 103 as being unpatentable over Brimert in view of Kay.
Brimert teaches as set forth above, the deprotection reaction which was done in one step (one addition of base instead of two consecutive additions). Kay teaches as set forth above.
It would have been obvious to one of ordinary skill in the art at the time the application was filed to carry out Brimert’s deprotection reaction and to add a second aliquot of base followed by additional stirring. The skilled artisan would have checked to see if the deprotection was complete, and if not, the skilled artisan would have added more reagent and allowed more time to achieve a complete reaction. The skilled artisan would have used an inert atmosphere for the reaction because sodium methoxide is a sensitive reagent which reacts vigorously with water and can ignite spontaneously in moist air. The skilled artisan would have optimized the temperature of the reaction using routine experimentation to provide an acceptable rate of reaction versus formation of side products, as set forth above.
Response to Arguments
Applicant argues that Brimert does not suggest making the reaction take place at elevated temperature, and Kay also fails to teach the temperature conditions. This argument is not persuasive because, as set forth above, the skilled artisan would have optimized the temperature of the reaction using routine experimentation to provide an acceptable rate of reaction versus formation of side products.
Applicant argues that the present inventors tried and failed to arrive at an upscalable process until arriving at the instantly claimed process. This argument is not persuasive because establishing long-felt need requires objective evidence that an art recognized problem existed in the art for a long period of time without solution. MPEP 716.04. Long-felt need is analyzed as of the date the problem is identified and articulated, and there is evidence of efforts to solve that problem. In this instance, there is no objective evidence on the record that an art recognized problem existed in the art for a long period of time without solution. Arguments presented by the applicant cannot take the place of evidence in the record. MPEP 716.01(c).
Applicant argues that the prior art does not suggest obtaining the claimed suitable process for upscaling, which produces the product in high yield and high purity. This argument is not persuasive because the claims do not require any particular yield or purity. To the extent that Applicant is arguing that scalability is an unexpected result of the claimed process, the burden is on applicant to establish that results are unexpected and significant. MPEP 716.02(b). The evidence relied upon should establish “that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance.” There is no evidence on the record that the claimed process is unexpectedly and significantly better than the prior art process. Furthermore, Applicants have the burden of explaining the data in any declaration they proffer as evidence of non-obviousness. There is no declaration in this instance. Finally, evidence of unexpected properties may be in the form a direct or indirect comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims. Applicant must identify the cause of the unexpectedly superior property (compared to the prior art) and establish a nexus for that cause. There is no comparison with the closest prior art on the record in this instance.
Applicant argues that Brimert does not disclose or suggest raising the temperature of the reaction. This argument is not persuasive because Brimert raises the temperature in several examples with other substrates. The skilled artisan would have expected that the temperature could be optimized because Brimert did reactions at increased temperature.
Applicant argues that the skilled artisan would not have increased the temperature because increased temperature could lead to decomposition. This argument is not persuasive because Brimert teaches that the temperature was increased in several analogous reactions.
Applicant argues that the prior art does not indicate that the temperature increase would result in an improved and scalable system. There is no evidence on the record that the prior art process was not scalable. The prior art yield was 60.5% after HPLC purification over two steps (page 136), and the current specification states that the yield was 65% over two steps, but not with HPLC purification. Any differences between the claimed invention and the prior art may be expected to result in some differences. The issue is whether the properties differ to such an extent that the difference is really unexpected. MPEP 716.02. In this instance, the process in the specification was not subjected to HPLC purification, which would have been expected to only decrease the yield, not increase the yield because material is being removed. The prior art yield and the current application’s yield are close (65% versus 60.5%), with the current application yield possibly higher than it would have been if the process was directly comparable with the prior art process. Applicants must show that the results were greater than those which would have been expected from the prior art to an unobvious extent. MPEP 716.02(a). In this instance, the small difference in yield could be attributable to routine optimization of the reaction. It is not at all clear that the yield is greater to an unobvious extent.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAYLA D BERRY whose telephone number is (571)272-9572. The examiner can normally be reached 7:00-3:00 CST, M-F.
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, Scarlett Goon can be reached on 571-270-5241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LAYLA D BERRY/ Primary Examiner, Art Unit 1693
Prosecution Insights