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 .
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 29 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.
Regarding claim 29, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 39 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Bristol-Myers Squibb Company (WO2024/020084A1, 2024-01-25) referred to herein as Bristol-Myers.
Bristol-Myers teach a compound having the name tert-butyl 6-chloro-4-[[(lR)-l-cyanoethyl]amino]pyridine-3-carboxylate 4’ which appears to correlate with the structure:
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(paragraph 00670).
Note: STN structure search of RN3027833-11-7 having the structure:
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appears to “hit” within this document at page 241 A-29-I. However, no structure can be found.
Claim(s) 22, 24-25, 34-35 and 37-38 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gilead Sciences, INC (WO2020/014468A1, 2020-01-16) referred to herein as Gilead.
Gilead teach a compound having the formula
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or pharmaceutically acceptable salt thereof (claim 5). Moreover, Gilead teaches a synthesis of 4-(((R)-l-cyanoethyl)amino)-6-(3-cyanopyrrolo[l,2-b]pyridazin-7-yl)-N-((R)-2-fluoro-3- hydroxy-3-methylbutyl)nicotinamide comprising the following reactions:
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(page 49, Example 3). While the initial reaction conditions appear to comprise microwave radiation, the WO document is silent on whether the cross coupling reaction requires microwave radiation. As such, it is presumed that such reaction does not occur in the presence of microwave radiation.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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 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) 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gilead Sciences, INC (WO2020/014468A1, 2020-01-16) referred to herein as Gilead, as applied to claims 22, 24-25, 34-35 and 37-38 above, in view of Buskes and Blanco (Molecules 2020; 25(15): 3493).
Gilead teach a compound having the formula
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or pharmaceutically acceptable salt thereof (claim 5). Moreover, Gilead teaches a synthesis of 4-(((R)-l-cyanoethyl)amino)-6-(3-cyanopyrrolo[l,2-b]pyridazin-7-yl)-N-((R)-2-fluoro-3- hydroxy-3-methylbutyl)nicotinamide comprising the following reactions:
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(page 49, Example 3).
Gilead does not specifically teach the reaction conditions for the cross-coupling reaction, specifically the solvent system being 2-methyltetrahydrofuran and water or the temperature of the reaction at 70-80oC.
Buskes and Blanco review the impact of cross-coupling reactions in drug discovery and development (Title). Specifically, Buskes and Blanco reviews the impact of this cross-coupling reaction in process chemistry during the scale-up and the trend in the industry to develop more “green” or environmentally friendly conditions such as using a biphasic reaction medium composed of 2-methyltetrahydrofuran and water to assist in solubilizing the base (page 8, Section 4).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify or optimize the conditions for the cross-coupling reaction used by Gilead such as by using a biphasic reaction medium composed of 2-methyltetrahydrofuran and water and optimize the temperature in view of the teachings of Buskes and Blanco. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
-Buskes and Blanco reviews the impact of this cross-coupling reaction in process chemistry during the scale-up and the trend in the industry to develop more “green” or environmentally friendly conditions such as using a biphasic reaction medium composed of 2-methyltetrahydrofuran and water to assist in solubilizing the base.
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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Claim(s) 28-33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gilead Sciences, INC (WO2020/014468A1, 2020-01-16) referred to herein as Gilead, as applied to claims 22, 24-25, 34-35 and 37-38 above, in view of Bose and Jayalakshmi (Synthesis 1999; 1: 64-65).
Gilead teach a compound having the formula
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or pharmaceutically acceptable salt thereof (claim 5). Moreover, Gilead teaches a synthesis of 4-(((R)-l-cyanoethyl)amino)-6-(3-cyanopyrrolo[l,2-b]pyridazin-7-yl)-N-((R)-2-fluoro-3- hydroxy-3-methylbutyl)nicotinamide comprising the following reactions:
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(page 49, Example 3).
Gilead does not specifically teach that the dehydration step utilizing an agent other than trifluoroacetic anhydride such as trifluoromethanesulfonic anhydride.
Bose and Jayalakshmi teach a practical method for the preparation of nitriles from primary amides under non-acidic conditions (Title). In particular, Bose and Jayalakshmi teach that the dehydration of primary amides proceeded efficiently in good yields at room temperature with trifluoromethanesulfonic anhydride and triethylamine within a few minutes, wherein no strong dehydration or longer reaction times is needed and the reaction can be easily carried out on a large scale (page 64, 2nd column, 1st full paragraph).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute TFAA and pyridine as taught by Gilead for trifluoromethanesulfonic anhydride and triethylamine for the dehydration reaction in view of the teachings of Bose and Jayalakshmi. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
Bose and Jayalakshmi teach that the dehydration of primary amides proceeded efficiently in good yields at room temperature with trifluoromethanesulfonic anhydride and triethylamine within a few minutes, wherein no strong dehydration or longer reaction times is needed and the reaction can be easily carried out on a large scale.
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 conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 3 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13-15 of copending Application No. 18759283 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application claims a
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which anticipates the citric acid salt of claim 3 of the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Therefore, Claims 3, 22, 24-26, 28-35 and 37-39 are rejected.
Claims 23 is 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.
Claims 1-2, 4-21, 27 and 36 are free of the prior art. The closest prior art to the instant claims is considered to be either Bristol-Myers Squibb Company (WO2024/020084A1, 2024-01-25) or Gilead Sciences, INC (WO2020/014468A1, 2020-01-16) both of which describe the synthesis of
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, but differ by the starting material and/or the reaction conditions. In particular, neither of the references utilize a compound of formula III or IV. Moreover, while a laundry list of pharmaceutical salts are contemplated in the Gilead WO documents, there is no specific teaching or suggestion to specifically select the citric acid salt. Lastly, regarding the claim 27, it is well known in the art that an organic base such as triethylamine or pyridine are used in combination with TFAA in the amide dehydration step. There is no suggestion or teachings of using either no base or an inorganic base.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRANDON J FETTEROLF whose telephone number is (571)272-2919. The examiner can normally be reached M-F 6AM-4PM.
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, Jeffrey S Lundgren can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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BRANDON J. FETTEROLF, PHD
Primary Patent Examiner
Art Unit 1626
/BRANDON J FETTEROLF/Primary Examiner, Art Unit 1626
Prosecution Insights