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 05/03/2024, is a continuation of U.S. provisional application No. 18/371,626 filed on 09/22/2023, which is a continuation of U.S. Patent Application No. 17/671,714, filed 02/15/2022, which claims priority to U.S. provisional application No. 63/149,901, filed on 02/16/2021 and U.S. provisional application No. 63/275,163 filed on 11/03/2021.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 11/14/2024, 07/02/2025 and 12/12/2025, 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.
DETAILED ACTION
The amendment and Applicant arguments filed on 12/12/2025 have been received and have been fully considered.
Claims 1, 29-30 and 40-41, claims 2-4, 7-9, 27-28, 31-32 and 34-39 were cancelled and claims 10-26, and 42-109 were previously cancelled. Claims 1, 5-6, 29-30, 33 and 40-41 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 form”
Claims 35 and 36 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Withdrawn Objection to Specification
Objection to the specification for containing embedded hyperlinks, is withdrawn in view of Applicant amendment to the specification filed on 12/12/2025, that deleted the embedded hyperlinks.
Objection to the specification for typographical error with regard to Application No. 17/671,714, is withdrawn in view of Applicant amendment to the specification filed on 12/12/2025, that corrected the error.
Rejections - Withdrawn
Withdrawn Claim Rejections - 35 USC § 102
Rejection to claims 1-9, and 27-36 under 35 U.S.C. 102(a)(2) as being anticipated by M. Vasbinder et al. (US 2022/0162196 A1, 05/26/2022), is withdrawn in view of Applicant amendment filed on 12/12/2025 that amended independent claim 1 with
Rejections – Maintained/Modified in view of the Amendments
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 non-obviousness.
35 USC § 103 over Vasbinder II in view of Khadka
Claims 1, 5-6, 29-30, 33 and 40-41 are rejected under 35 U.S.C. 103 as being unpatentable over M. Vasbinder et al. (US PG-PUB 2022/0162196 A1, 05/26/2022, (effective filing date 04/28/2020) “Vasbinder II” cited in the previous PTO-892 dated 08/13/2025) in view of P. Khadka et al. (Asian Journal of Pharmaceutical Sciences, Volume 9, Issue 6, 2014, Pages 304-316, ISSN 1818-0876, “Khadka” cited in the previous PTO-892 dated 08/13/2025).
Prior art effect of Vasbinder II
The applied reference, Vasbinder II, has a common Assignee and Inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02. 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. This will be applied to this 102 and the following103 rejections herein.
Vasbinder II discloses a method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of PARP7 inhibitor, compound 1 (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), [Pg. 7, [0094] and claims 1 and 23 and 24]:
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Vasbinder II discloses that compound 1 or salts and solid forms thereof can be administered in the form of pharmaceutical compositions of Compound 1 or salts and solid forms thereof, and at least one pharmaceutically acceptable carrier, wherein the composition in the form of tablets or pills and can be administered orally, [Pg. 9, [0112]- [0113]]. Vasbinder II discloses examples wherein compound 1 is administered orally once and twice a day at a dose of 500 mg. [Pg. 20, [0180]-[0181]]. Vasbinder II discloses that compound 1 is also administered in doses of 62.5, 125, 250 and 500 mg. [Pg. 20, [0180]].
However, Vasbinder II does not teach that the compound or pharmaceutically acceptable salt has a particle size diameter of about 5 to about 30 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.].
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 II’s compound 1 above to less than 30 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 improves solubility and increases the bioavailability of drugs, and provides guidance to different particle size reduction technologies that produce drug particle size as low as 5-10 µm. Thus, claims 1, 40 and 41 are obvious over Vasbinder II and Khadka.
Claim 33 is met because Vasbinder II discloses that cancer is associated with overexpression or activity of PARP7, wherein the cancers include breast, central nervous system, endometrium, kidney, large intestine, lung, esophagus, ovary, pancreas, prostate, stomach, head and neck (upper aerodigestive), urinary tract, colon, etc. [Pg. 7, [0095]-Pg. 8, [0097]].
With regard to claims 5, 6, 29, 30, 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 II’s dosing range of 0.1-500 mg of PARP7 inhibitor to about 400 mg, 600 mg, 200 mg, 300 mg daily doses of the PARP7 inhibitor measured as free base in view of the teachings of Vasbinder II. One of ordinary skill in the art is motivated to do so with reasonable expectation of success because Vasbinder II discloses that compound 1 is administered at doses of 125, 250 and 500 mg twice daily [Pg. 20, [0180], [0181]]; Vasbinder II discloses that compound 1 can be subdivided into unit dosage forms containing from 0.1 to about 500 mg [Pg. 9, [0116]]; Vasbinder II discloses that compound 1 can be effective over a wide dosage range; Vasbinder II discloses that compound 1 is administered in a pharmaceutically effective amount that 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. 9, [0115]].
Moreover, Vasbinder II discloses dosing ranges that encompasses and overlapped with the claims’ ranges, and 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).” Thus, claims 5, 6, 29, 30 are obvious over Vasbinder II.
35 USC § 103 over Vasbinder in view of Khadka
Claims 1, 5-6, 29-30, 33, and 40-41 are rejected under 35 U.S.C. 103 as being unpatentable over M. Vasbinder et al. (US PG-PUB 2019/0330194 A1, 10/31/2019, “Vasbinder” cited in the previous PTO-892 dated 08/13/2025) in view of P. Khadka et al. (Asian Journal of Pharmaceutical Sciences, Volume 9, Issue 6, 2014, Pages 304-316, ISSN 1818-0876, “Khadka” cited in the previous PTO-892 dated 08/13/2025).
Vasbinder teaches a method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an agent that inhibits PARP7 activity, such as a compound of Formula I, or a pharmaceutically acceptable salt thereof. [0013]. Vasbinder teaches the claimed compound as 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 that the cancer is associated with abnormal expression or activity of PARP7, wherein the cancers include multiple myeloma, DLBCL, hepatocellular carcinoma, bladder cancer, esophageal cancer, head and neck cancer (upper aerodigestive cancer), kidney cancer, prostate cancer, rectal cancer, stomach cancer, thyroid cancer, uterine cancer, and breast cancer. [Pg. 29, [0524]-[0527]].
Vasbinder teaches pharmaceutical formulations and dosage forms of the above PARP7 inhibitor and pharmaceutical excipient, wherein the formulation is for oral administration, wherein the composition can be formulated in a unit dosage form, wherein 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, [0540], [542], [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 μg/kg to about 1 g/kg of body weight per day; 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; and 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]].
Vasbinder teaches that the PARP7 inhibitors, i.e., compound 664, are administered once or twice daily. [Pg. 397, [2117]].
As such, Vasbinder teaches a method of treating cancer associated with overexpression of PARP7 comprising administering dose ranges of about 0.01 mg/kg to about 100 mg/kg, and 0.1 to about 500 mg administered once or twice daily. 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 dosing range of 0.1 mg to about 500 mg of the PARP7 inhibitor above, Vasbinder does not teach that the daily dosage is about 400-600 mg, or the subdivided doses of 200 mg, 300 mg, 400 mg or 600 mg. Vasbinder does not teach that the compound of pharmaceutically acceptable salt has a particle size diameter 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.].
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 above to about 5 to about 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.
With regard to the claimed daily dosage of about 400-600 mg, or the subdivided doses of 200 mg, 300 mg, 400 mg or 600 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 400-600 mg, or the subdivided doses of 200 mg, 300 mg, 400 mg or 600 mg 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).” Thus, claims 1, 5, 6, 29, 30, 33, 40 and 41 are obvious over Vasbinder and Khadka
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. Indeed, Khadka teaches that modern particle technologies now seek to reduce the particle size of active pharmaceutical ingredients to the nanometer size range. 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. In other words, one skilled in the art would not have had a reasonable expectation that the administration of Compound 1 or a pharmaceutically acceptable salt thereof, wherein the particle size diameter [d90] of the compound is about 5 to about 15µm, would result in significantly increased bioavailability. In contrast to the cited art, the application as filed discloses the unexpected result that when comparing formulations containing nonmicronized (d[90] of about 228.474 µm) with micronized (d[90] of about 10.851 µm) 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 unit dosage form recited in the claims 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. These advantageous clinical properties could not have been predicted at the time of filing.
Examiner response:
Applicant’s arguments have been fully considered but they are not persuasive for the following reasons. In response to applicant's assertion that Khadka teaches to reduce particle size below 1 mm, and Applicant statement that “based on the disclosure of Khadka, one of ordinary skill in the art would expect that a particle size of less than 1 µm would be necessary to improve solubility and bioavailability”, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
There is no explicit or implicit teaching of Khadka to specifically reduce the particle size to 1 µm. Khadka’s document includes many particle size reduction techniques, one of which is jet milling. Instant specification recites that “the compound of Formula I used in the dosage forms of the invention is micronized. The micronized drug substance can be prepared, for example, by jet milling. “[page 8, ln. 14-15]. Khadka describes many advantages of jet milling technique that produces micronized particle size of 5-10 µm, including improvement of dissolution rate while avoiding disadvantages of conventional micronization such as agglomeration, poor flowability, loss of expected large surface area, low bulk density and insignificant or no dissolution improvement [page 307, col. 2, last para.]. Thus, one of ordinary skill in the art would have been motivated to utilized Khadka’s jet milling technique and decrease the size of the PARP7 inhibitor (compound 1 taught by Vasbinder II or compound 664 taught by Vasbinder). One of ordinary skill in the art would have reasonable expectation that decreasing the particle size for example, to 10 µm would result in significant increase in bioavailability because Khadka teaches that micronize the particle to 5-10 µm increase dissolution due to increased particle surface area. [page 308, col. 1, 1st para.]. Obviousness does not require absolute predictability, but a reasonable expectation of success. See MPEP 2143.02.
With regard to Applicant argument regarding 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, according to Khadka document, the increase in bioavailability is expected. Khadka teaches that reducing the particle size is a common approach to increase drug solubility, and conventional size reduction methods used for formulating drugs with poor aqueous solubility are summarized in Fig. 1 and Table 2. [page 306, col. 1, 1st para.]. Khadka teaches that all micronization methods of size reduction have been reported in various studies to have increased the dissolution and bioavailability of poorly aqueous soluble drugs by decreasing their size and increasing the surface area of the drugs. [page 307, col. 2, 1st para.]. Khadka teaches that in one study, powders were micronized to the particle size range of 5-10 µm through the process of simultaneous micronization, and the increase in dissolution behavior is attributed to the increased particle surface area [page 308, col. 1, 1st para.]. Khadka teaches that High pressure homogenization (HPH) produces micronized products that can be directly recovered in the form of a dry powder as suggested by Kluge et al., wherein HPH has been reported to improve the dissolution rate and bioavailability [page 308, col. 2, last para.]. Khadka teaches that HPH is useful in oral as well as parenteral drug formulations and is remarkably efficient in enhancing saturation solubility, dissolution as well as bioavailability of poorly soluble drugs. [page 309, col. 1, 2nd para.]. Khadka teaches that in another study, spray freezing into cryogenic liquids (SFL) has also been proved to be successful in preparing oral and pulmonary formulations of drugs like danazol and itraconazole by enhancing the dissolution rates and thus increasing bioavailability of these drugs in animal experiments [page 310, col. 1, 1st para]. Khadka teaches that ball mill, a mechanical micronization method [Tale 2], produces a single homogenous amorphous phase with higher dissolution rates compared to the same drugs prepared by spray drying, [page 308, col. 2, 1st para.]. In view of the foregoing, the claimed improving bioavailability and increase in AUC and Cmax is expected and it was not surprising that the claimed reduction in size to about 5-15 µm increases the bioavailability of Vasbinder’s/Vasbinder II’s compound. Therefore, the asserted unexpected results is insufficient to overcome the rejection of Vasbinder’s/Vasbinder II’s in view of Khadka.
Applicant argues:
Vasbinder discloses over example 700 compounds having PARP7 inhibitory activity. The Office has not pointed to any reason why one of ordinary skill in the art, based on the disclosure of Vasbinder, would have selected 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 (the compound of Example 664 of Vasbinder) for further development. Moreover, 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. 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. Even if one of ordinary skill in the art were to arrive at the claimed subject matter based on the disclosure of Vasbinder and Khadka, which Applicant disagrees, one of ordinary skill in the art would not have had a reasonable expectation that the unit dosage form recited in the claims would exhibit its favorable clinical properties (e.g., the disclosed AUC and Cmax values) or be suitable for clinical development.
Examiner response:
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). Vasbinder provide motivation to one of ordinary skill in the art to pick compound 664 out of all PARP7 inhibitors disclosed in Vasbinder patent application because Vasbinder picks only compound 664 and all Vasbinder claims are directed to only one compound, compound 664. Thus, one of ordinary skill in the art have access to Vasbinder and looking to use a PARP7 inhibitor for treating cancer related to PARP7 activity, would be motivated to pick the compound 664. Because obviousness does not require absolute predictability, but a reasonable expectation of success See MPEP 2143.02, by only picking compound 664, Vasbinder would provide reasonable expectation that compound 664 would be potent PARP7 inhibitor. Applicant’s argument that Vasbinder does not mention solubility or bioavailability data for any compound, is not commensurate with the claim scope. However, as discussed above, Khadka teaches that particle size reduction is well known for enhance drug bioavailability and dissolution rate, which would motivate skilled artisan looking to utilize Vasbinder’s compound in a method of treating cancer associate with PARP7 to decrease the particle size e.g., 10 µm. Therefore, Applicant’s arguments are not persuasive.
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 1, 5-6, 29-30, 33, and 40-41 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, “Filloon” cited in the previous PTO-892 dated 08/13/2025); Remington's Pharmaceutical science, 18th edition, Gennaro, A.R., ED, Mack Pub. Co.: Easton, PA, 1990, pp 1633-1665, “Remington”, cited in the previous PTO-892 dated 08/13/2025) and P. Khadka et al. (Asian Journal of Pharmaceutical Sciences, Volume 9, Issue 6, 2014, Pages 304-316, ISSN 1818-0876, “Khadka” cited in the previous PTO-892 dated 08/13/2025). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1, 5-6, 29-30, 33 and 40-41 recites “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 pharmaceutically acceptable salt thereof, is administered at a total daily dosage of about 100, 200, 300, 400, 500, 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 µm, wherein the cancer is a breast cancer, a cancer of the central nervous system, an endometrium cancer, a kidney cancer, a large intestine cancer, a lung cancer:
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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 the use of the above compound for treating cancer; the amount of the above compound in the pharmaceutical composition is about 400 mg to about 600 mg; or particle size diameter of about 5 to about 15 µm.
US Patent No. 10,550,105 B2 specification recite a method of using the above compound in treating cancer, wherein the cancer is associated with abnormal expression or activity of PARP7, wherein the cancers include multiple myeloma, DLBCL, hepatocellular carcinoma, bladder cancer, esophageal cancer, head and neck cancer (upper aerodigestive cancer), kidney cancer, prostate cancer, rectal cancer, stomach cancer, thyroid cancer, uterine cancer, and breast cancer. [Pg. 40, col. 54, ln. 10-45].
MPEP 804 states: The specification can be used as a dictionary to learn the meaning of a term in the claim. Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999) ("[W]ords in patent claims are given their ordinary meaning in the usage of the field of the invention, unless the text of the patent makes clear that a word was used with a special meaning."); Renishaw PLC v. Marposs Societa' per Azioni, 158 F.3d 1243, 1250, 48 USPQ2d 1117, 1122 (Fed. Cir. 1998) ("Where there are several common meanings for a claim term, the patent disclosure serves to point away from the improper meanings and toward the proper meanings."). "The Patent and Trademark Office (‘PTO’) determines the scope of the claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction ‘in light of the specification as it would be interpreted by one of ordinary skill in the art.’ " Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) (en banc) (quoting In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364, 70 USPQ2d 1827, 1830 (Fed. Cir. 2004); see also MPEP § 2111.01. Further, those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (as distinguished from an obvious variation of the subject matter disclosed in the reference patent or application). In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970). The court in Vogel recognized "that it is most difficult, if not meaningless, to try to say what is or is not an obvious variation of a claim," but that one can judge whether or not the invention claimed in an application is an obvious variation of an embodiment disclosed in the patent or application which provides support for the claim. According to the court, one must first "determine how much of the patent disclosure pertains to the invention claimed in the patent" because only "[t]his portion of the specification supports the patent claims and may be considered." The court pointed out that "this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined." In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010); Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008); Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003).
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 respect 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., 400mg-600mg 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).”
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 US Patent No. 10,550,105 B2 compound above to about 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 1, 5-6, 29-30, 33 and 40-41 are obvious over US Patent No. 10,550,105 B2, Remington, Filloon and Khadka.
Double Patenting over U.S. Patent No. 10,870,641 B2
Claims 1, 5-6, 29-30, 33, and 40-41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 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, “Filloon” cited in the previous PTO-892 dated 08/13/2025); Remington's Pharmaceutical science, 18th edition, Gennaro, A.R., ED, Mack Pub. Co.: Easton, PA, 1990, pp 1633-1665, “Remington”, cited in the previous PTO-892 dated 08/13/2025) and P. Khadka et al. (Asian Journal of Pharmaceutical Sciences, Volume 9, Issue 6, 2014, Pages 304-316, ISSN 1818-0876, “Khadka” cited in the previous PTO-892 dated 08/13/2025). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1, 5-6, 29-30, 33 and 40-41 recites “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 pharmaceutically acceptable salt thereof, is administered at a total daily dosage of about 100, 200, 300, 400, 500, 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 µm, wherein the cancer is a breast cancer, a cancer of the central nervous system, an endometrium cancer, a kidney cancer, a large intestine cancer, a lung cancer:
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U.S. Patent No. 10,870,641 B2 recites in conflicting claims 1-30 “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 recites that said cancer is breast cancer, cancer of the central nervous system, endometrium cancer, kidney cancer, large intestine cancer, lung cancer, oesophagus cancer, ovarian cancer, pancreatic cancer, prostate cancer, stomach cancer, head and neck cancer (upper aerodigestive cancer), urinary tract cancer, or colon cancer.
US Patent No. 10,870,641 B2 does not recite in claims 1-30 that the therapeutically effective amount is an amount of about 400 mg to about 600 mg; or particle size diameter of about 5 to about 15 µm.
The teachings of Remington, Filloon and Khadka are as discussed above.
The obviousness rationale is like the obviousness rationale for the Double Patenting Rejection of claims 1, 5-6, 29-30, 33 and 40-41 above, page 16, and is incorporated herein by reference as applied to the rejected claims.
Double Patenting over U.S. Patent No. 11,014,913 B2
Claims 1, 5-6, 29-30, 33, and 40-41 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, “Filloon” cited in the previous PTO-892 dated 08/13/2025); Remington's Pharmaceutical science, 18th edition, Gennaro, A.R., ED, Mack Pub. Co.: Easton, PA, 1990, pp 1633-1665, “Remington”, cited in the previous PTO-892 dated 08/13/2025) and P. Khadka et al. (Asian Journal of Pharmaceutical Sciences, Volume 9, Issue 6, 2014, Pages 304-316, ISSN 1818-0876, “Khadka” cited in the previous PTO-892 dated 08/13/2025). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1, 5-6, 29-30, 33 and 40-41 recites “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 pharmaceutically acceptable salt thereof, is administered at a total daily dosage of about 100, 200, 300, 400, 500, 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 µm, wherein the cancer is a breast cancer, a cancer of the central nervous system, an endometrium cancer, a kidney cancer, a large intestine cancer, a lung cancer:
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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 the use of the above compound for treating cancer; the amount of the above compound in the pharmaceutical composition is about 400 mg to about 600 mg; or particle size diameter of about 5 to about 15 µm.
US Patent No. 11,014,913 B2 specification recite a method of using the above compound in treating cancer, wherein the cancer is associated with abnormal expression or activity of PARP7, wherein the cancers include multiple myeloma, DLBCL, hepatocellular carcinoma, bladder cancer, esophageal cancer, head and neck cancer (upper aerodigestive cancer), kidney cancer, prostate cancer, rectal cancer, stomach cancer, thyroid cancer, uterine cancer, and breast cancer. [Pg. 40, col. 54, ln. 33-64].
MPEP 804 states: The specification can be used as a dictionary to learn the meaning of a term in the claim. Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999) ("[W]ords in patent claims are given their ordinary meaning in the usage of the field of the invention, unless the text of the patent makes clear that a word was used with a special meaning."); Renishaw PLC v. Marposs Societa' per Azioni, 158 F.3d 1243, 1250, 48 USPQ2d 1117, 1122 (Fed. Cir. 1998) ("Where there are several common meanings for a claim term, the patent disclosure serves to point away from the improper meanings and toward the proper meanings."). "The Patent and Trademark Office (‘PTO’) determines the scope of the claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction ‘in light of the specification as it would be interpreted by one of ordinary skill in the art.’ " Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) (en banc) (quoting In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364, 70 USPQ2d 1827, 1830 (Fed. Cir. 2004); see also MPEP § 2111.01. Further, those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (as distinguished from an obvious variation of the subject matter disclosed in the reference patent or application). In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970). The court in Vogel recognized "that it is most difficult, if not meaningless, to try to say what is or is not an obvious variation of a claim," but that one can judge whether or not the invention claimed in an application is an obvious variation of an embodiment disclosed in the patent or application which provides support for the claim. According to the court, one must first "determine how much of the patent disclosure pertains to the invention claimed in the patent" because only "[t]his portion of the specification supports the patent claims and may be considered." The court pointed out that "this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined." In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010); Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008); Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003).
The teachings of Remington, Filloon and Khadka are as discussed above.
The obviousness rationale is like the obviousness rationale for the Double Patenting Rejection of claims 1, 5-6, 29-30, 33 and 40-41 above, page 16, and is incorporated herein by reference as applied to the rejected claims.
Double Patenting over U.S. Patent No. 11,566,020 B1
Claims 1, 5-6, 29-30, 33, and 40-41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 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, “Filloon” cited in the previous PTO-892 dated 08/13/2025); Remington's Pharmaceutical science, 18th edition, Gennaro, A.R., ED, Mack Pub. Co.: Easton, PA, 1990, pp 1633-1665, “Remington”, cited in the previous PTO-892 dated 08/13/2025) and P. Khadka et al. (Asian Journal of Pharmaceutical Sciences, Volume 9, Issue 6, 2014, Pages 304-316, ISSN 1818-0876, “Khadka” cited in the previous PTO-892 dated 08/13/2025). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1, 5-6, 29-30, 33, and 40-41 recites “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 pharmaceutically acceptable salt thereof, is administered at a total daily dosage of about 100, 200, 300, 400, 500, 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 µm, wherein the cancer is a breast cancer, a cancer of the central nervous system, an endometrium cancer, a kidney cancer, a large intestine cancer, a lung cancer:
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U.S. Patent No. 11,566,020 B1 recites in conflicting claims 1-15 “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, wherein said cancer is breast cancer, cancer of the central nervous system, endometrium cancer, kidney cancer, large intestine cancer, lung cancer, oesophagus cancer, ovarian cancer, pancreatic cancer, prostate cancer, stomach cancer, head and neck cancer (upper aerodigestive cancer), urinary tract cancer, or colon cancer:
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US Patent No. 11,566,020 B1 does not recite in claims 1-30 that the therapeutically effective amount is an amount of about 400 mg to about 600 mg; or particle size diameter of about 5 to about 15 µm.
The teachings of Remington, Filloon and Khadka are as discussed above.
The obviousness rationale is like the obviousness rationale for the Double Patenting Rejection of claims 1, 5-6, 29-30, 33 and 40-41 above, page 16, and is incorporated herein by reference as applied to the rejected claims.
Double Patenting over U.S. Patent No. 12371421 B2
Claims 1, 5-6, 29-30, 33 and 40-41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 17-20 of U.S. Patent No. 12371421 B2 in view of Filloon TG. Stat Med. 1995 May 15-30;14(9-10):925-32; discussion 933, “Filloon” cited in the previous PTO-892 dated 08/13/2025); Remington's Pharmaceutical science, 18th edition, Gennaro, A.R., ED, Mack Pub. Co.: Easton, PA, 1990, pp 1633-1665, “Remington”, cited in the previous PTO-892 dated 08/13/2025) and P. Khadka et al. (Asian Journal of Pharmaceutical Sciences, Volume 9, Issue 6, 2014, Pages 304-316, ISSN 1818-0876, “Khadka” cited in the previous PTO-892 dated 08/13/2025). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1, 5-6, 29-30, 33 and 40-41 recites “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 pharmaceutically acceptable salt thereof, is administered at a total daily dosage of about 100, 200, 300, 400, 500, 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 µm, wherein the cancer is a breast cancer, a cancer of the central nervous system, an endometrium cancer, a kidney cancer, a large intestine cancer, a lung cancer:
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U.S. Patent No. 12371421 B2 recites in conflicting claims 1, and 17-20 “A method of treating cancer in a patient in need of treatment comprising administering to said patient a therapeutically effective amount of a solid form of Compound 1, wherein said cancer is breast cancer, cancer of the central nervous system, endometrium cancer, kidney cancer, large intestine cancer, lung cancer, esophagus cancer, ovarian cancer, pancreatic cancer, prostate cancer, stomach cancer, head and neck cancer upper aerodigestive cancer, urinary tract cancer, or colon cancer:
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US Patent No. 12371421 B2 does not recite in claims 1 and 17-20 that the therapeutically effective amount is an amount of about 400 mg to about 600 mg; or particle size diameter of about 5 to about 15 µm.
The teachings of Remington, Filloon and Khadka are as discussed above.
The obviousness rationale is like the obviousness rationale for the Double Patenting Rejection of claims 1, 5-6, 29-30, 33 and 40-41 above, page 16, and is incorporated herein by reference as applied to the rejected claims.
Double Patenting over copending Application No. 18/371,626
Note: Statutory Double Patenting over claim 1-9 and 27-41 is modified to a Nonstatutory Double Patenting in view of the amendment to the copending Application No. 18/371,626 filed on 10/14/2025 that cancelled claim 1-41, and amended claim 42.
Claims 1, 5-6, 29-30, 33 and 40-41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 42-51 and 56-57 of copending Application No. 18/371,626 (US PG-PUB 2024/0325391 A1) in view of Filloon TG. Stat Med. 1995 May 15-30;14(9-10):925-32; discussion 933, “Filloon” cited in the previous PTO-892 dated 08/13/2025). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1, 5-6, 29-30, 33 and 40-41 recites “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 pharmaceutically acceptable salt thereof, is administered at a total daily dosage of about 100, 200, 300, 400, 500, 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 µm, wherein the cancer is a breast cancer, a cancer of the central nervous system, an endometrium cancer, a kidney cancer, a large intestine cancer, a lung cancer:
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copending Application No. 18/371,626 recited in conflicting claims 42-51 and 56-57 “a unit dosage form comprising 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, 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.
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copending Application No. 18/371,626 does not recite in claims 42-51 and 56-57 the use of the above compound for treating cancer; the amount of the above compound in the pharmaceutical composition is about 400 mg to about 600 mg administered twice daily.
copending Application No. 18/371,626 specification recite a method of using the above compound in treating cancer, wherein the cancer is associated with abnormal expression or activity of PARP7, wherein the cancers include multiple myeloma, DLBCL, hepatocellular carcinoma, bladder cancer, esophageal cancer, head and neck cancer (upper aerodigestive cancer), kidney cancer, prostate cancer, rectal cancer, stomach cancer, thyroid cancer, uterine cancer, and breast cancer. [Pg. 1, ln. 20-23, pg. 14, ln. 15-19].
MPEP 804 states: The specification can be used as a dictionary to learn the meaning of a term in the claim. Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999) ("[W]ords in patent claims are given their ordinary meaning in the usage of the field of the invention, unless the text of the patent makes clear that a word was used with a special meaning."); Renishaw PLC v. Marposs Societa' per Azioni, 158 F.3d 1243, 1250, 48 USPQ2d 1117, 1122 (Fed. Cir. 1998) ("Where there are several common meanings for a claim term, the patent disclosure serves to point away from the improper meanings and toward the proper meanings."). "The Patent and Trademark Office (‘PTO’) determines the scope of the claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction ‘in light of the specification as it would be interpreted by one of ordinary skill in the art.’ " Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) (en banc) (quoting In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364, 70 USPQ2d 1827, 1830 (Fed. Cir. 2004); see also MPEP § 2111.01. Further, those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (as distinguished from an obvious variation of the subject matter disclosed in the reference patent or application). In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970). The court in Vogel recognized "that it is most difficult, if not meaningless, to try to say what is or is not an obvious variation of a claim," but that one can judge whether or not the invention claimed in an application is an obvious variation of an embodiment disclosed in the patent or application which provides support for the claim. According to the court, one must first "determine how much of the patent disclosure pertains to the invention claimed in the patent" because only "[t]his portion of the specification supports the patent claims and may be considered." The court pointed out that "this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined." In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010); Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008); Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003).
With respect to administering the above compound twice daily, Filloon teaches detailed description on determining the minimum therapeutically effective dose, the lowest dose level that yields a therapeutic benefit to patients.
With regard to the total daily dose of 400-600 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 copending Application No. 18/371,626 dose range of about 25 mg to about 500 mg of PARP7 inhibitor to about 400-600 mg (e.g., 200 mg, 300 mg twice daily) of the PARP7 inhibitor measured as free base. One of ordinary skill in the art is motivated to do so with reasonable expectation of success because copending Application No. 18/371,626 range encompasses and overlapped with the claims’ ranges, and 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).”
One of ordinary skill in the art would have been motivated to administer copending Application No. 18/371,626 compound twice daily because Filloon teaches how to determine the therapeutically effective dose, Filloon teaches that one or two doses are administer during and twice a day (BID) dosing is administered in all Filloon’s studies, wherein all the treatments were taken twice daily during determining the therapeutically effective dose and tolerance analysis, [pg. 928, Figures 1-4]. Copending Application No. 18/371,626 is silent with respect to dosing frequency of the 25-500 mg e.g., twice daily, thus, Filloon would reasonably provide motivation to skill artisan practicing copending Application No. 18/371,626 above compound to admonishing the compound twice daily. Thus, claims 1, 5-6, 29-30, 33 and 40-41 are obvious over copending Application No. 18/371,626 in view of Filloon.
Conclusion
Claims 1, 5-6, 29-30, 33, and 40-41 are rejected. No claim is allowed.
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/M.M.A./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622