CTNF 18/684,747 CTNF 82948 Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Election/Restrictions PNG media_image1.png 62 552 media_image1.png Greyscale Claims 155-182 are examined together. Claim Rejections - 35 USC § 103 07-20-aia AIA 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. 07-21-aia AIA Claim s 155-182 are rejected under 35 U.S.C. 103 as being unpatentable over Wrobleski J. Med. Chem. 2019, 62, 8973-8995; Zhang WO2018183656; Roberts WO2019232138 and WO2020251911 further in view of Morissette, Advanced Drug Delivery Reviews 56 (2004) 275-300 and Rodriguez, Advanced Drug Delivery Reviews 56 (2004) 241-274 . Wrobleski teaches crystalline form of the instant free base compound. Reference to this is found at page 8981 column B, last line and at page 8982 column A 6 th line from bottom. Diffraction parameters of protein bound compound 11 (which is the instant compound) is found in the Wrobleski Supplementary materials. Wrobleski is silent with regards to diffraction parameters for the above noted crystalline free base. Zhang also discloses the crystalline compound, see front page for the Figure of the diffraction pattern. Robert also teaches different crystalline polymorphs, see front pages of ‘138 and ‘911. These references teach how to make different polymorphs of the same compound by using different crystallization conditions. The why and how of making different polymorphs of active pharmaceutical compounds in general are taught in Morissette and Rodriguez. As Morissette concludes with the advent of high throughput crystallization methods, appreciation for the landscape of physical form for drug development has begun to change. Use of these systems has the potential to facilitate drug development by saving valuable time in selecting the optimal physical or chemical form of a given compound. As such there is nothing surprising (see specification page 2, lines 20-23) in arriving at different forms of crystals. Based on the teachings of the cited references that given different polymorphs provide opportunity for arriving at different crystalline forms of the compounds of the known API, there is nothing unobvious in the claims. Several crystalline forms of the recited compound are described in the prior art (Wrobleski, Zhang and Roberts). Morissette and Rodriguez summarize the impetus of and the benefit of synthesizing as many polymorphs as possible of any active pharmaceutical ingredient of interest, the traditional difficulties, and technological means of overcoming these difficulties. Even if the prior art polymorphs are not identical to Applicant’s claimed/recited polymorphs, it would have nonetheless been obvious to the person of ordinary skill in the art to follow the teachings of Morissette and Rodriguez, and obtain Applicant’s claimed/recited polymorphs. The person of ordinary skill in the art would have had a reasonable expectation of successfully obtaining Applicant’s claimed/recited polymorphs by using high throughput technology which permits the person of ordinary skill in the art to evaluate thousands of crystallization experiments in parallel and identify all polymorphs of a particular active agent. A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02). Further, consider the utility of the different polymorphic forms (including that of Wrobleski and Zhang) of the compound. There is common ground that the biological activity of a compound depends primarily on its molecular structure. To reach its target it will at some point be in solution, e.g. in body fluids, where all differences among polymorphs disappear. The skilled person would thus expect that all polymorphs of the compound display the same pharmacodynamic profile. In addition, the methods to screen for polymorphs are well known in the art as taught by Morissette and Rodriguez. The skilled person being investigating the therapeutic application of the compound would thus routinely screen for polymorphs thereof. If such routine work yields other polymorphs, e.g. the presently claimed ones, then their provision is an obvious . 07-96 AIA The prior art made of record and not relied upon is considered pertinent to applicant's disclosure : Gardner, Application of high throughput technologies to drug substance and drug product development, Computers and Chemical Engineering 2004, 28, 943-953 . Double Patenting 08-33 AIA 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. 08-34 AIA Claim s 155-182 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 1-13 of U.S. Patent No. 12570637 further view of Wrobleski J. Med. Chem. 2019, 62, 8973-8995; Zhang WO2018183656; Roberts WO2019232138 and WO2020251911; Morissette, Advanced Drug Delivery Reviews 56 (2004) 275-300 and Rodriguez Advanced Drug Delivery Reviews 56 (2004) 241-274 . Although the claims at issue are not identical, they are not patentably distinct from each other because the claims contain overlapping subject matter as explained below: The difference is in the different polymorphic forms of the instant claims as ascertained by the recited diffraction parameters. Arriving at different crystalline forms of the same compound and ascertaining their X-ray diffraction parameters are routine to one of skill in the art engaged in making alternate versions of prior art crystals. The secondary references teach why and how for this as explained below: Wrobleski teaches crystalline form of the instant free base compound. Reference to this is found at page 8981 column B, last line and at page 8982 column A 6 th line from bottom. Diffraction parameters of protein bound compound 11 (which is the instant compound) is found in the Wrobleski Supplementary materials. Wrobleski is silent with regards to diffraction parameters for the above noted crystalline free base. Zhang also discloses the crystalline compound, see front page for the Figure of the diffraction pattern. Robert also teaches different crystalline polymorphs, see front pages of ‘138 and ‘911. These references teach how to make different polymorphs of the same compound by using different crystallization conditions. The why and how of making different polymorphs of active pharmaceutical compounds in general are taught in Morissette and Rodriguez. As Morissette concludes with the advent of high throughput crystallization methods, appreciation for the landscape of physical form for drug development has begun to change. Use of these systems has the potential to facilitate drug development by saving valuable time in selecting the optimal physical or chemical form of a given compound. As such there is nothing surprising (see specification page 2, lines 20-23) in arriving at different forms of crystals. Based on the teachings of the cited references that given different polymorphs provide opportunity for arriving at different crystalline forms of the compounds of the known API, there is nothing unobvious in the claims. Several crystalline forms of the recited compound are described in the prior art (Wrobleski, Zhang and Roberts). Morissette and Rodriguez summarize the impetus of and the benefit of synthesizing as many polymorphs as possible of any active pharmaceutical ingredient of interest, the traditional difficulties, and technological means of overcoming these difficulties. Even if the prior art polymorphs are not identical to Applicant’s claimed/recited polymorphs, it would have nonetheless been obvious to the person of ordinary skill in the art to follow the teachings of Morissette and Rodriguez, and obtain Applicant’s claimed/recited polymorphs. The person of ordinary skill in the art would have had a reasonable expectation of successfully obtaining instantly claimed/recited polymorphs by using high throughput technology which permits the person of ordinary skill in the art to evaluate thousands of crystallization experiments in parallel and identify all polymorphs of a particular active agent. Further, consider the utility of the different polymorphic forms (including that of 12570637, Wrobleski and Zhang) of the compound. There is common ground that the biological activity of a compound depends primarily on its molecular structure. To reach its target it will at some point be in solution, e.g. in body fluids, where all differences among polymorphs disappear. The skilled person would thus expect that all polymorphs of the compound display the same pharmacodynamic profile. In addition, the methods to screen for polymorphs are well known in the art as taught by Morissette and Rodriguez. The skilled person being investigating the therapeutic application of the compound would thus routinely screen for polymorphs thereof. If such routine work yields other polymorphs, e.g. the presently claimed ones, then their provision is an obvious . 08-35 AIA Claim s 155-182 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 57-69, 72-74, 93, 94 of copending Application No. 18284531 (reference application) further view of Wrobleski J. Med. Chem. 2019, 62, 8973-8995; Zhang WO2018183656; Roberts WO2019232138 and WO2020251911; Morissette, Advanced Drug Delivery Reviews 56 (2004) 275-300 and Rodriguez Advanced Drug Delivery Reviews 56 (2004) 241-274 . Although the claims at issue are not identical, they are not patentably distinct from each other because the claims contain overlapping subject matter as explained below: The difference is in the different polymorphic forms of the instant claims as ascertained by the recited diffraction parameters. Arriving at different crystalline forms of the same compound and ascertaining their X-ray diffraction parameters are routine to one of skill in the art engaged in making alternate versions of prior art crystals. The secondary references teach why and how for this as explained below: Wrobleski teaches crystalline form of the instant free base compound. Reference to this is found at page 8981 column B, last line and at page 8982 column A 6 th line from bottom. Diffraction parameters of protein bound compound 11 (which is the instant compound) is found in the Wrobleski Supplementary materials. Wrobleski is silent with regards to diffraction parameters for the above noted crystalline free base. Zhang also discloses the crystalline compound, see front page for the Figure of the diffraction pattern. Robert also teaches different crystalline polymorphs, see front pages of ‘138 and ‘911. These references teach how to make different polymorphs of the same compound by using different crystallization conditions. The why and how of making different polymorphs of active pharmaceutical compounds in general are taught in Morissette and Rodriguez. As Morissette concludes with the advent of high throughput crystallization methods, appreciation for the landscape of physical form for drug development has begun to change. Use of these systems has the potential to facilitate drug development by saving valuable time in selecting the optimal physical or chemical form of a given compound. As such there is nothing surprising (see specification page 2, lines 20-23) in arriving at different forms of crystals. Based on the teachings of the cited references that given different polymorphs provide opportunity for arriving at different crystalline forms of the compounds of the known API, there is nothing unobvious in the claims. Several crystalline forms of the recited compound are described in the prior art (Wrobleski, Zhang and Roberts). Morissette and Rodriguez summarize the impetus of and the benefit of synthesizing as many polymorphs as possible of any active pharmaceutical ingredient of interest, the traditional difficulties, and technological means of overcoming these difficulties. Even if the prior art polymorphs are not identical to Applicant’s claimed/recited polymorphs, it would have nonetheless been obvious to the person of ordinary skill in the art to follow the teachings of Morissette and Rodriguez, and obtain Applicant’s claimed/recited polymorphs. The person of ordinary skill in the art would have had a reasonable expectation of successfully obtaining instantly claimed/recited polymorphs by using high throughput technology which permits the person of ordinary skill in the art to evaluate thousands of crystallization experiments in parallel and identify all polymorphs of a particular active agent. Further, consider the utility of the different polymorphic forms (including that of 18284531, Wrobleski and Zhang) of the compound. There is common ground that the biological activity of a compound depends primarily on its molecular structure. To reach its target it will at some point be in solution, e.g. in body fluids, where all differences among polymorphs disappear. The skilled person would thus expect that all polymorphs of the compound display the same pharmacodynamic profile. In addition, the methods to screen for polymorphs are well known in the art as taught by Morissette and Rodriguez. The skilled person being investigating the therapeutic application of the compound would thus routinely screen for polymorphs thereof. If such routine work yields other polymorphs, e.g. the presently claimed ones, then their provision is an obvious . This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. 07-96 AIA The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Feldman, Understanding ‘Evergreening’ : Making Minor Modifications Of Existing Medications To Extend Protections, Health Affairs June 2022 41:6, 801-804 Dwivedi, Evergreening: A deceptive device in patent rights, Technology in Society 32, (2010) 324–330. Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIZAL S CHANDRAKUMAR whose telephone number is (571)272-6202. The examiner can normally be reached M-F 8-5 EST. 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, Andrew Kosar can be reached at (571) 272-0913. 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. /NIZAL S CHANDRAKUMAR/Primary Examiner, Art Unit 1625 Application/Control Number: 18/684,747 Page 2 Art Unit: 1625 Application/Control Number: 18/684,747 Page 3 Art Unit: 1625 Application/Control Number: 18/684,747 Page 4 Art Unit: 1625 Application/Control Number: 18/684,747 Page 5 Art Unit: 1625
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