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 .
Priority
This application, filed on 09/22/2023, is a continuation of U.S. Patent Application No. 17/671,714, filed 02/15/2022, which claims priority to U.S. provisional application 63/149,901, filed on 02/16/2021 and 63/275,163 filed on 11/03/2021.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 01/27/2025, complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits, except where noted.
Election/Restriction
Applicant’s election of Group II, pending claims 42-57, without traverse in the reply filed on 01/27/2025 to Restriction Requirement filed on 11/25/2024, is acknowledged. Claims 1-41 and 58-109 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made with traverse in the reply filed on 01/27/2025. After careful reconsideration, claims 71-82 are rejoined. Thus, claims 1-41, 58-70, and 83-109 are withdrawn, and claims 42-57 and 71-82 are under consideration.
Status of Claims
Applicant’s amendment and arguments filed on 10/14/2025 have been received and have been carefully considered.
Claims 42, 56-57 and 76 were amended, and claims 1-41, 52-55, 58-75, 78-80 and 83-109 were cancelled.
Claims 42-51, 56-57, 76-77 and 81-82 are pending.
Claim Interpretation
Examination requires claim terms first be construed in terms in the broadest reasonable manner during prosecution as is reasonably allowed in an effort to establish a clear record of what applicant intends to claim. See MPEP § 2111. Under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. See MPEP § 2111.01. It is also appropriate to look to how the claim term is used in the prior art, which includes prior art patents, published applications, trade publications, and dictionaries. MPEP § 2111.01 (III). However, specific embodiments of the specification cannot be imported into the claims, particularly where the subject claim limitation is broader than the embodiment. MPEP § 2111.01(II).
Claim interpretation for “unit dosage”
Claims 42-57 recite “a unit dosage form”. The unit dosage will be interpreted as a pharmaceutical composition, for example a capsule or tablet.
Withdrawn Objection to Specification
Objection to the disclosure for containing an embedded hyperlink, and typographical error, is withdrawn in view of Applicant’s amendment to the Specification filed on 10/14/2025, that amended the Specification by removing the hyperlink and correcting the typo with Application No. 17/671,714.
Withdrawn Claim Rejections - 35 USC § 103
Rejection of claims 42-52 and 76-77 under 35 U.S.C. 103 as being unpatentable over M. Vasbinder et al. (US 20190330194 A1, 10/31/2019), is withdrawn in view of Applicant’s amendment filed on 10/14/2025, that amended claim 1 with “wherein the unit dosage form is in the form of a tablet, and wherein the particle size diameter [d90] of the compound, or pharmaceutically acceptable salt thereof, is about 5 to about 15 um.”
Rejection Maintained/Modified
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 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.
35 USC § 103 over Vasbinder in view of Khadka
Claims 42-51, 56-57, 76-77 and 81-82 are rejected under 35 U.S.C. 103 as being unpatentable over M. Vasbinder et al. (US 20190330194 A1, 10/31/2019, “Vasbinder” cited in the PTO-892 dated 04/15/2025) in view of P. Khadka et al. (Asian Journal of Pharmaceutical Sciences, Volume 9, Issue 6, 2014, Pages 304-316, ISSN 1818-0876, doi.org/10.1016/j.ajps.2014.05.005, “Khadka” cited in the PTO-892 dated 04/15/2025).
Vasbinder teaches a pharmaceutical composition comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier, wherein the claimed compound discloses as a species of Formula I in Table E11 [Pg. 370, Table E11, Ln. 1], and in Vasbinder’s claims 444-451, as Vasbinder document claims the compound and its pharmaceutical compositions:
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Vasbinder teaches pharmaceutical formulations and dosage forms of the above PARP7 inhibitor, [540], wherein the formulation is for oral administration, wherein the composition can be formulated in a unit dosage form, a physically discrete unit suitable as unitary dosages for human subjects and other mammals, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect, in association with a suitable pharmaceutical excipient. [Pg. 30, [542]]. Vasbinder teaches that the unit dosage form is prepared in a solid composition including tablets, pills and capsules containing 0.1 to about 500 mg of the above compound [Pg. 30, [0544]].
Vasbinder teaches that the therapeutic dosage can vary according to, for example, the particular use for which the treatment is made, the manner of administration of the compound, the health and condition of the patient, and the judgment of the prescribing physician, and the amount can vary depending upon a number of factors including dosage, chemical characteristics, and the route of administration. Some typical dose ranges are from about 1 mg/kg to about 1 g/kg of body weight per day. In some embodiments, the dose range is from about 0.01 mg/kg to about 100 mg/kg of body weight per day. The dosage is likely to depend on the type and extent of progression of the disease or disorder, the overall health status of the particular patient, the relative biological efficacy of the compound selected, formulation of the excipient, and its route of administration. Effective doses can be extrapolated from dose-response curves derived from in vitro or animal model test systems. [Pg. 31, 0550]].
Vasbinder teaches that the active compound can be effective over a wide dosage range and is generally administered in a pharmaceutically effective amount. It will be understood, however, that the amount of the compound actually administered will usually be determined by a physician according to the relevant circumstances, including the condition to be treated, the chosen route of administration, the actual compound administered, the age, weight, and response of the individual patient, the severity of the patient's symptoms, and the like. [Pg. 31, [0548]].
As such, Vasbinder teaches dose ranges of about 0.01 mg/kg to about 100 mg/kg, and 0.1 to about 500 mg. Note that Vasbinder does not provide numerical values to the relative term “about”, nevertheless, Vasbinder teaches that the term “about” indicate that the value or range of values may deviate to an extent deemed reasonable to one of ordinary skill in the art. [Pg. 26, [509]].
However, while Vasbinder teaches a unit dosage form, tablets, for oral administration containing 0.1 to about 500 mg of the PARP7 inhibitor above, Vasbinder does not teach that the dosage form in an amount of about 25 mg to about 500 mg, or the subdivided doses of 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 250 mg, or 300 mg. Vasbinder does not teach that the solid PARP7 inhibitor has a particle size diameter [d90] of about 5 to about 15 µm.
Khadka teaches that the particle size reduction is one of the oldest strategies for improving solubility of drugs since solubility of drugs is intrinsically related to drug particle size, and when the particle size is decreased, the larger surface area of the drug allows the increase in the surface area to volume ratio thus increasing the surface area available for solvation. Khadka teaches that the particle size reduction technologies are therefore routinely used to increase the bioavailability of poorly soluble drugs. [Khadka, pg. 306, col. 1]. Khadka teaches that particle size reduction techniques involving powder and particle technology including mechanical micronization such as jet milling, ball milling, homogenization, which can produce particle size range of 5-10 µm. [Pg. 307- 308, col. 1, 1st para.].
With regard to the amount of about 25-500 mg, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective failing date of the instant claimed invention to modify Vasbinder’s dosing range of 0.1-500 mg of PARP7 inhibitor to dosages of about 25 mg- about 500 mg or 30%-50% of the PARP7 inhibitor measured as free base in view of the teachings of Vasbinder. One of ordinary skill in the art is motivated to do so with reasonable expectation of success because Vasbinder teaches dosing ranges that encompasses and overlapped with the claims’ ranges and teaches that the administered amount will be determine by the prescribing physician according to many factors including the manner of administration, the type and extent of progression of the disease or disorder, the overall health status of the particular patient, and response of the individual patient and the like. As provided in the MPEP 2144.05, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). See also In re Harris, 409 F.3d 1339, 74 USPQ2d 1951 (Fed. Cir. 2005). Moreover, MPEP 2144.05.II.A explains: “Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration 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).”
With regard to the particle size diameter [d90] of about 5 to about 15 µm, 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 decrease the particle size of Vasbinder’s compound 664 5-15 µm, i.e., 10 µm in view of the teachings of Khadka. One of ordinary skill would have been motivated to do so with reasonable expectation of success because Khadka teaches that particle size reduction improving solubility and increase the bioavailability of drugs, and provide guidance to different particle size reduction technologies that produce drug particle size as low as 5-10 µm.
Thus, claims 42-51, 56-57 and 81-82 are obvious over Vasbinder and Khadka.
With regard to claims 76 and 77 Vasbinder teaches that for preparing solid compositions such as tablets, the principal active ingredient is mixed with a pharmaceutical excipient to form a solid pre-formulation composition e.g., unit dosage containing a homogeneous mixture of a PARP7 inhibitor, wherein the unit dosage forms of the type described above containing from, for example, 0.1 to about 500 mg of the active ingredient of the PARP7 inhibitor. Vasbinder teaches that in the unit dosage form, the active compound can be effective over a wide dosage range and is generally administered in a pharmaceutically effective amount. It will be understood, however, that the amount of the compound actually administered will usually be determined by a physician, according to the relevant circumstances, including the age, weight, and response of the individual patient, the severity of the patient's symptoms, and the like. [Pg. 30, [0544]].
Response to arguments
Applicant argues:
Khadka indicates that "Williams et al. (2013) and Sun et al. (2012) have separately reported that particle size reduction indeed has effects on the kinetic solubility of the substance and according to Ostwalf-Freundlich Equation, the solubility increases significantly on reducing particle size below 1 pm (0.5 pm in radius). This is because the reduction of size below 1 pm increases solvation pressure, giving rise to an increase on solubility and also causes disruption of solute- solute interaction which eases the solubilization process" (emphasis added). See Khadka at page 306. Thus, based on the disclosure of Khadka, one of ordinary skill in the art would expect that a particle size of less than 1 pm would be necessary to improve solubility and bioavailability.
Examiner response:
Applicant’s arguments have been fully considered but they are not persuasive for the following reasons. Applicant argues that Khadka stated that reduction in size below 1 mm significantly increases solubility, and that Khadka would motivate a person of ordinary skill in the art to target nanoparticle sizes instead of a microparticle size of 5-10 µm. However, Khadka explicitly teaches “micronized to the particle size range of 5-10 µm through the process of simultaneous micronization. The increase in dissolution behavior is attributed to the increased particle surface area, as per the NoyeseWhitney equation.” Khadka explicitly teaches micronization as the conventional technique for particle size reduction to increase solubility of drugs. Khadka explains in detail the processes of drug micronization include mechanical micronization, jet milling, ball milling, high pressure homogenization. The fact that Khadka also teaches nanoparticles alongside microparticles [see page 313, col. 1, 3rd para.], does not preclude the ordinary skilled artisan from utilizing Khadka’s micronization, specifically because Khadka provided the ordinary skilled artisan with the micronization techniques needed to increase drug solubility and bioavailability. Prior art references are relevant as prior art for all they contain and “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). "A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994),” see MPEP 2123.
Applicant argues:
the application as filed discloses the unexpected result that when comparing formulations containing non-micronized (d[90] of about 228.474 pm) with micronized (d[90] of about 10.851 pm) 5-[[(2S)-1-(3-oxo-3-[4-[5-(trifluoromethy]l)pyrimidin-2- yl]piperazin-1-yl]propoxy )propan-2-yl]amino]-4-(trifluoromethyl )-2,3-dihydropyridazin-3-one in human patients, the mean AUC increased by about 1.5-fold and the mean Cmax increased by about 2.4-fold for the formulations containing the micronized compound. This represents a significant increase in bioavailability in human patients that could not have been expected at the time of filing. Moreover, the claimed unit dosage form/solid pharmaceutical formulation has exhibited a tolerable safety profile in human patients with solid tumors and is currently being evaluated in Phase lb/2 clinical trials, which are described at Example E of the specification as filed. The advantageous clinical properties of the claimed unit dosage form and pharmaceutical formulation could not have been predicted at the time of filing. Vasbinder does not mention solubility or bioavailability data for any compound, much less the compound of Example 664, or suggest that the bioavailability of the compound might be a concern. Khadka does not mention any PARP7 inhibitors, much less the compound recited in the claims. Thus, it is unclear why one skilled in the art would have combined the disclosure of Vasbinder and Khadka. Taken together, it appears that the Office is relying on impermissible hindsight to formulate the obviousness rejection.
Examiner response:
Applicant’s arguments have been fully considered but they are not persuasive for the following reasons. It appears that Applicant is attempting to show unexpected results. As provided in MPEP 716 (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." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992). "[A]ppellants have the burden of explaining the data in any declaration they proffer as evidence of non-obviousness." Ex parte Ishizaka, 24 USPQ2d 1621, 1624 (Bd. Pat. App. & Inter. 1992). However, applicant argument with respect to increase in bioavailability is not statistical and practical significance because it’s known in the art that reduction in size increases solubility, dissolution and bioavailability, [see Khadka Abstract, and page 306, col. 1]. Khadka teaches in many examples, an increase of dissolution as much as 20-fold compared to commercial tablets. Khadka teaches that “particle size reduction is one of the oldest strategies for improving solubility of drugs since solubility of drugs is intrinsically related to drug particle size. When the particle size is decreased, the larger surface area of the drug allows the increase in the surface area to volume ratio thus increasing the surface area available for solvation. Particle size reduction technologies are therefore routinely used to increase the bioavailability of poorly soluble drugs. As such, Applicant asserted unexpected results appear to be insufficient and expected in view of the prior art, and it was not surprising that decreasing the particle size of Vasbinder’s compound to 5-10 µm as taught by Khadka will increase Cmax and AUC.
Applicant’s specification provides Study Drug Supply, wherein the claimed compound is administered to dogs in micronized and non-micronized forms. [Instant specification, page 24-25]. The compound was administered at a dose of 100 mg and particle size dimeter d90 of 10.851 µm. The pharmacokinetic analysis of administering the tablets micronized and non-micronized to dogs at 100 mg and 10.851 µm is shown to increase Cmax and AUC (Group D vs Group E) [see instant specification, page 28, Table 2]. Applicant does not explain why a 2.8-fold increase in AUC and 4.7-fold increase in Cmax is considered significant because, as discussed above, an increase in bioavailability, Cmax and AUC is expected in view of Khadka. Moreover, Applicant’s results reflecting 100 mg and 10.851 µm. As provided in MPEP 716 (d), “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." However, Applicant does not show how one of ordinary skill in the art would predict that an amount of 25-500 mg of the claimed compound having the claimed particle size dimeter would produce similar significant results. One of ordinary skill in the art would not have reasonable expectation to predict that a dosage amount that is 0.25 or 5 times the tested amount would produce same results. Therefore, it appears that the unexpected result is not commensurate in scope with respect to the scope of the claimed unit dosage form.
With respect to applicant impermissible hindsight arguments, In response to applicant's argument that the examiner's conclusion of obviousness is based upon 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).
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Double Patenting over U.S. Patent No. 10,550,105 B2
Claims 42-51, 56-57, 76-77 and 81-82 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 10,550,105 B2 in view of Filloon TG. Stat Med. 1995 May 15-30;14(9-10):925-32; discussion 933. doi: 10.1002/sim.4780140911., “Filloon” cited in the PTO-892); Remington's Pharmaceutical science, 18th edition, Gennaro, A.R., ED, Mack Pub. Co.: Easton, PA, 1990, pp 1633-1665, “Remington”, cited in the PTO-892) and P. Khadka et al. (Asian Journal of Pharmaceutical Sciences, Volume 9, Issue 6, 2014, Pages 304-316, ISSN 1818-0876, doi.org/10.1016/j.ajps.2014.05.005, “Khadka” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant claims 42-51, 56-57, 76-77 and 81-82 recite “a unit dosage form comprising 5-[[(2S)-1-(3-oxo-3-[4-[5- (trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]propoxy)propan-2-yl] amino]-4-(trifluoromethyl)-2,3-dihydropyridazin-3-one, or a pharmaceutically acceptable salt thereof, in an amount of about 25 mg to about 500 mg, measured as the free base, wherein the unit dosage form is in the form of a tablet, and wherein the particle size diameter [d90] of the compound, or pharmaceutically acceptable salt thereof, is about 5 to about 15 um, and a solid pharmaceutical formulation comprising the compound of claim 42, or a pharmaceutically acceptable salt thereof, in an amount of about 30% to about 50% w/w (e.g., 40%), and at least one pharmaceutically acceptable excipient.” The structure of claims 42 compound is shown below:
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US Patent No. 10,550,105 B2 recited in conflicting claims 1-4 “a pharmaceutical composition comprising a compound having the structure below, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier:
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US Patent No. 10,550,105 B2 does not recite in claims 1-4 that the amount of the above compound in the pharmaceutical composition is about 25 mg to about 500 mg, or the subdivided doses of 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 250 mg, or 300 mg, and does not teach that the solid PARP7 inhibitor has a particle size diameter [d90] of about 5 to about 15 µm.
With respect to preparing a solid pharmaceutical composition of the pharmaceutically active compound above, Remington teaches that pharmaceutical active substances are most frequently administered orally in a solid dosage form including tablets and capsules and teaches the preparation method of the solid dosage form. [Abstract].
With respect to the amount of the pharmaceutically active compound above in the solid dosage form, Filloon teaches detailed description on determining the minimum therapeutically effective dose, the lowest dose level that yields a therapeutic benefit to patients. Thus, the determination of a therapeutically effective dose of a known pharmaceutical active agent is routine in the prior art.
With regard to the particle size, Khadka teaches that the particle size reduction is one of the oldest strategies for improving solubility of drugs since solubility of drugs is intrinsically related to drug particle size, and when the particle size is decreased, the larger surface area of the drug allows the increase in the surface area to volume ratio thus increasing the surface area available for solvation. Khadka teaches that the particle size reduction technologies are therefore routinely used to increase the bioavailability of poorly soluble drugs. [Khadka, pg. 306, col. 1]. Khadka teaches that particle size reduction techniques involving powder and particle technology including mechanical micronization such as jet milling, ball milling, homogenization, which can produce particle size range of 5-10 µm. [Pg. 307- 308, col. 1, 1st para.].
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective failing date of the instant claimed invention to prepare a solid oral dosage form of the therapeutically active compound taught by US Patent No. 10,550,105 B2 in a therapeutically effective amount e.g., 25mg-500mg in view of the teachings of Remington and Filloon. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because US Patent No. 10,550,105 B2 teaches that the compound is used for the treatment of cancer which indicates that the compound is a therapeutically active compound; Remington teaches methods of preparing a solid oral dosage form of pharmaceutically active compounds and provide motivation to prepare them in solid oral dosage form; and Filloon teaches how to determine the minimum therapeutically effective dose. Therefore, one of ordinary skill in the art would have been motivated to utilize the teachings of Remington and Filloon to prepare therapeutic effective amount of the US Patent No. 10,550,105 B2 above compound in an oral dosage form. Moreover, MPEP 2144.05.II.A explains: “Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration 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).”
With regard to the particle size diameter [d90] of about 5 to about 15 µm, 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 decrease the particle size of Vasbinder’s compound 664 5-15 µm, i.e., 10 µm in view of the teachings of Khadka. One of ordinary skill would have been motivated to do so with reasonable expectation of success because Khadka teaches that particle size reduction improving solubility and increase the bioavailability of drugs, and provide guidance to different particle size reduction technologies that produce drug particle size as low as 5-10 µm.
Double Patenting over U.S. Patent No. 10,870,641 B2
Claims 42-51, 56-57, 76-77 and 81-82 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 16 of U.S. Patent No. 10,870,641 B2 in view of Filloon TG. Stat Med. 1995 May 15-30;14(9-10):925-32; discussion 933. doi: 10.1002/sim.4780140911., “Filloon” cited in the PTO0892), Remington's Pharmaceutical science, 18th edition, Gennaro, A.R., ED, Mack Pub. Co.: Easton, PA, 1990, pp 1633-1665, “Remington”, cited in the PTO-892) and P. Khadka et al. (Asian Journal of Pharmaceutical Sciences, Volume 9, Issue 6, 2014, Pages 304-316, ISSN 1818-0876, doi.org/10.1016/j.ajps.2014.05.005, “Khadka” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant claims 42-51, 56-57, 76-77 and 81-82 recite “a unit dosage form comprising 5-[[(2S)-1-(3-oxo-3-[4-[5- (trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]propoxy)propan-2-yl] amino]-4-(trifluoromethyl)-2,3-dihydropyridazin-3-one, or a pharmaceutically acceptable salt thereof, in an amount of about 25 mg to about 500 mg, measured as the free base, wherein the unit dosage form is in the form of a tablet, and wherein the particle size diameter [d90] of the compound, or pharmaceutically acceptable salt thereof, is about 5 to about 15 um, and a solid pharmaceutical formulation comprising the compound of claim 42, or a pharmaceutically acceptable salt thereof, in an amount of about 30% to about 50% w/w (e.g., 40%), and at least one pharmaceutically acceptable excipient.” The structure of claims 42 compound is shown below:
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U.S. Patent No. 10,870,641 B2 recites in conflicting claims 1 and 16 “a method of treating cancer in a patient in need of treatment comprising administering to said patient a therapeutically effective amount of a compound having the structure:
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US Patent No. 10,870,641 B2 does not recite in claims 1 or 16 that the therapeutically effective amount is an amount of about 25 mg to about 500 mg, or the subdivided doses of 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 250 mg, or 300 mg, and does not teach that the solid PARP7 inhibitor has a particle size diameter [d90] of about 5 to about 15 µm.
The teachings of Filloon, Remington and Khadka are as discussed above.
The obviousness rationale is like the obviousness rationale for the Double Patenting Rejection of claims above, page 15 and is incorporated herein by reference as applied to the rejected claims.
Double Patenting over U.S. Patent No. 11,014,913 B2
Claims 42-51, 56-57, 76-77 and 81-82 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 13 of U.S. Patent No. 11,014,913 B2 in view of Filloon TG. Stat Med. 1995 May 15-30;14(9-10):925-32; discussion 933. doi: 10.1002/sim.4780140911, “Filloon” cited in the PTO0892), Remington's Pharmaceutical science, 18th edition, Gennaro, A.R., ED, Mack Pub. Co.: Easton, PA, 1990, pp 1633-1665, “Remington”, cited in the PTO-892) and P. Khadka et al. (Asian Journal of Pharmaceutical Sciences, Volume 9, Issue 6, 2014, Pages 304-316, ISSN 1818-0876, doi.org/10.1016/j.ajps.2014.05.005, “Khadka” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant claims 42-51, 56-57, 76-77 and 81-82 recite “a unit dosage form comprising 5-[[(2S)-1-(3-oxo-3-[4-[5- (trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]propoxy)propan-2-yl] amino]-4-(trifluoromethyl)-2,3-dihydropyridazin-3-one, or a pharmaceutically acceptable salt thereof, in an amount of about 25 mg to about 500 mg, measured as the free base, wherein the unit dosage form is in the form of a tablet, and wherein the particle size diameter [d90] of the compound, or pharmaceutically acceptable salt thereof, is about 5 to about 15 um, and a solid pharmaceutical formulation comprising the compound of claim 42, or a pharmaceutically acceptable salt thereof, in an amount of about 30% to about 50% w/w (e.g., 40%), and at least one pharmaceutically acceptable excipient.” The structure of claims 42 compound is shown below:
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U.S. Patent No. 11,014,913 B2 recites in conflicting claims 1 and 13 “a compound which is 5-[[(2S)-1-(3-oxo-3-[4-[5- (trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]propoxy)propan-2-yl] amino]-4-(trifluoromethyl)-2,3-dihydropyridazin-3-one, wherein the compound is crystalline, and a pharmaceutical composition comprising a compound of claim 1 and at least one pharmaceutically acceptable carrier:
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US Patent No. 11,014,913 B2 does not recite in claims 1 and 13 that the amount of the above compound in the pharmaceutical composition is about 25 mg to about 500 mg, or the subdivided doses of 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 250 mg, or 300 mg, and does not teach that the solid PARP7 inhibitor has a particle size diameter [d90] of about 5 to about 15 µm.
The teachings of Filloon, Remington and Khadka are as discussed above.
The obviousness rationale is like the obviousness rationale for the Double Patenting Rejection of claims above, page 15 and is incorporated herein by reference as applied to the rejected claims.
Double Patenting over U.S. Patent No. 11,566,020 B1
Claims 42-52 and 76-77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,566,020 B1 in view of Filloon TG. Stat Med. 1995 May 15-30;14(9-10):925-32; discussion 933. doi: 10.1002/sim.4780140911., “Filloon” cited in the PTO0892), Remington's Pharmaceutical science, 18th edition, Gennaro, A.R., ED, Mack Pub. Co.: Easton, PA, 1990, pp 1633-1665, “Remington”, cited in the PTO-892) and P. Khadka et al. (Asian Journal of Pharmaceutical Sciences, Volume 9, Issue 6, 2014, Pages 304-316, ISSN 1818-0876, doi.org/10.1016/j.ajps.2014.05.005, “Khadka” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant claims 42-51, 56-57, 76-77 and 81-82 recite “a unit dosage form comprising 5-[[(2S)-1-(3-oxo-3-[4-[5- (trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]propoxy)propan-2-yl] amino]-4-(trifluoromethyl)-2,3-dihydropyridazin-3-one, or a pharmaceutically acceptable salt thereof, in an amount of about 25 mg to about 500 mg, measured as the free base, wherein the unit dosage form is in the form of a tablet, and wherein the particle size diameter [d90] of the compound, or pharmaceutically acceptable salt thereof, is about 5 to about 15 um, and a solid pharmaceutical formulation comprising the compound of claim 42, or a pharmaceutically acceptable salt thereof, in an amount of about 30% to about 50% w/w (e.g., 40%), and at least one pharmaceutically acceptable excipient.” The structure of claims 42 compound is shown below:
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U.S. Patent No. 11,566,020 B1 recites in conflicting claim 1 “a method of treating cancer in a patient in need of treatment comprising administering to said patient a therapeutically effective amount of a compound which is 5-[[(2S)-1-(3-oxo-3-[4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]propoxy)propan-2-yl]amino]-4-(trifluoromethyl)-2,3-dihydropyridazin-3-one, wherein the compound is crystalline:
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US Patent No. 11,566,020 B1 does not recite in claim 1 that the therapeutically effective amount is an amount of about 25 mg to about 500 mg, or the subdivided doses of 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 250 mg, or 300 mg, and does not teach that the solid PARP7 inhibitor has a particle size diameter [d90] of about 5 to about 15 µm.
The teachings of Filloon, Remington and Khadka are as discussed above.
The obviousness rationale is like the obviousness rationale for the Double Patenting Rejection of claims above, page 15 and is incorporated herein by reference as applied to the rejected claims.
Double Patenting over U.S. Patent No. 12,371,421B2
Claims 42-52 and 76-77 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of US Patent No. 12371421B2 in view of Filloon TG. Stat Med. 1995 May 15-30;14(9-10):925-32; discussion 933. doi: 10.1002/sim.4780140911., “Filloon” cited in the PTO0892), Remington's Pharmaceutical science, 18th edition, Gennaro, A.R., ED, Mack Pub. Co.: Easton, PA, 1990, pp 1633-1665, “Remington”, cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant claims 42-51, 56-57, 76-77 and 81-82 recite “a unit dosage form comprising 5-[[(2S)-1-(3-oxo-3-[4-[5- (trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]propoxy)propan-2-yl] amino]-4-(trifluoromethyl)-2,3-dihydropyridazin-3-one, or a pharmaceutically acceptable salt thereof, in an amount of about 25 mg to about 500 mg, measured as the free base, wherein the unit dosage form is in the form of a tablet, and wherein the particle size diameter [d90] of the compound, or pharmaceutically acceptable salt thereof, is about 5 to about 15 um, and a solid pharmaceutical formulation comprising the compound of claim 42, or a pharmaceutically acceptable salt thereof, in an amount of about 30% to about 50% w/w (e.g., 40%), and at least one pharmaceutically acceptable excipient.” The structure of claims 42 compound is shown below:
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US Patent No. 12371421B2 recites in conflicting claims “a solid form of compound 1 having the formula below or a benzenesulfonic acid thereof, and a pharmaceutical composition comprising a compound of claim 1 and at least one pharmaceutically acceptable carrier:
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US Patent No. 12371421B2 does not recite that the amount of the above compound in the pharmaceutical composition is about 25 mg to about 500 mg, or the subdivided doses of 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 250 mg, or 300 mg, and does not teach that the solid PARP7 inhibitor has a particle size diameter [d90] of about 5 to about 15 µm.
The teachings of Filloon, Remington and Khadka are as discussed above.
The obviousness rationale is like the obviousness rationale for the Double Patenting Rejection of claims above, page 15 and is incorporated herein by reference as applied to the rejected claims.
Double Patenting over Copending application 18/654,312
Claims 42-51, 56-57, 76-77 and 81-82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 6, 29-30 and 40-41 of Copending application 18/654,312 (US 2025/0064803 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant claims 42-51, 56-57, 76-77 and 81-82 recite “a unit dosage form comprising 5-[[(2S)-1-(3-oxo-3-[4-[5- (trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]propoxy)propan-2-yl] amino]-4-(trifluoromethyl)-2,3-dihydropyridazin-3-one, or a pharmaceutically acceptable salt thereof, in an amount of about 25 mg to about 500 mg, measured as the free base, wherein the unit dosage form is in the form of a tablet, and wherein the particle size diameter [d90] of the compound, or pharmaceutically acceptable salt thereof, is about 5 to about 15 um, and a solid pharmaceutical formulation comprising the compound of claim 42, or a pharmaceutically acceptable salt thereof, in an amount of about 30% to about 50% w/w (e.g., 40%), and at least one pharmaceutically acceptable excipient.” The structure of claims 42 compound is shown below:
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Copending application 18/654,312 recites in the conflicting claims “a method for treating cancer in a subject, wherein the method comprises administering to the subject the compound 5-[[(2S)-1-(3-oxo-3-[4-[5-(trifluoromethyl)pyrimidin- 2-yl]piperazin- 1 -yl]propoxy)propan-2-yl]amino] -4-(trifluoromethyl)-2,3-dihydropyridazin-3- one, or a pharmaceutically acceptable salt thereof, at a total daily dosage of about 400 mg to about 600 mg, measured as the free base, wherein the compound, or the pharmaceutically acceptable salt thereof, is administered as an oral unit dosage form in the form of a tablet twice daily; and wherein the particle size diameter [d90] of the compound, or pharmaceutically acceptable salt thereof, is about 5 to about 15 um, wherein the compound, or pharmaceutically acceptable salt thereof, is administered at a total daily dosage of about 200 mg, 300 mg, 400 mg, or 600 mg measured as the free base, wherein the compound, or a pharmaceutically acceptable salt thereof, is administered orally, wherein the compound, or a pharmaceutically acceptable salt thereof, is administered as an oral unit dosage form, wherein the oral unit dosage form is in the form of a capsule or tablet:
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Copending application 18/654,312 dosage anticipates claims 42-51, 56-57, 76-77 and 81-82. Please note that Copending application 18/654,312 teaches therapeutic effective amount of the same compound for treating the same conditions, for example, instant claimed compound and Copending application 18/654,312 compound are directed to treating cancer.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant argues:
For all the aforementioned Non-Statutory Double Patenting rejections, Applicant argues that the claims as amended are nonobvious over U.S. Patent No. 10,550,105 B2 for at least the reasons discussed above.
Examiner response:
Applicant’s arguments have been fully considered but they are not persuasive for the reasons discussed above in the response for the argument with respect to obviousness rejection.
Conclusion
Claims 42-51, 56-57, 76-77 and 81-82 are rejected.
THIS ACTION IS MADE FINAL. 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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/M.M.A./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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