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 .
DETAILED ACTION
This office action is in response to applicant’s reply filed on August 14, 2026.
Status of Claims
Amendment of claims 1, 5-6, 8-10 and 25; cancellation of claims 4 and 7 and addition of claim 26 is acknowledged.
Claims 1-3, 5-6, 8-13, 15-17, 19-20, 23 and 25-26 are currently pending and are the subject of this office action.
Claims 1-3, 5-6, 8-13, 15-17, 19-20, 23 and 25-26 are presently under examination.
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Claim Rejections - 35 USC § 103 (New Rejection not Necessitated by Amendment).
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
1) Claim(s) 1-3, 5-6, 8-13, 15-17, 19-20, 23 and 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over ZENTALIS press release (April 12, 2021, cited by Applicant) in view of Huang et. al. (WO 2019/173082, 09/12/2019, cited by Applicant).
For claim 1-2, ZENTALIS teaches a method of treating Uterine Serous Carcinoma (USC) comprising the administration of a therapeutically effective amount of ZN-c3 ((R)-2-allyl-1-(7-ethyl-7-hydroxy-6,7-dihydro-5H- cyclopenta-[b]-pyridin-2-yl)-6-(4-methylpiperazin-1-yl)-phenyl)-amino)-1,2-dihydro-3H pyrazolo-[3,4-d]-pyrimidin-3-one, AZENOSERTIB) to a subject in need thereof.
ZENTALIS does not teach that the dosing regimen comprises intermittent dosing phase. However, Huang teaches that substituted 1,2-dihydro-3H-pyrazolo-[3,4-D]-pyrimidin-3-ones are effective in treating all different types of cancers including uterus body cancers, wherein the 1,2-dihydro-3H-pyrazolo-[3,4-D]-pyrimidin-3-one can be ZN-c3 (see abstract, paragraph [0138] and example 9B on page 70).
Huang further teaches:
“The desired dose may conveniently be presented in a single dose or as
divided doses administered at appropriate intervals, for example, as two, three, four or more sub-doses per day. The sub-dose itself may be further divided, e.g., into a number of discrete loosely spaced administrations” (see [0148]). “As will be readily apparent to one skilled in the art, the useful in vivo dosage to be administered and the particular mode of administration will vary depending upon the age, weight, the severity of the affliction, the mammalian species treated, the particular compounds employed and the specific use for which these compounds are employed. The determination of effective dosage levels, that is the dosage levels necessary to achieve the desired result, can be accomplished by one skilled in the art using routine methods, for example, human clinical trials, in vivo studies and in vitro studies” (see [0149]). ”Dosage amount and interval may be adjusted individually to provide plasma levels of the active moiety which are sufficient to maintain the modulating effects, or minimal effective concentration (MEC). The MEC will vary for each compound but can be estimated from in vivo and/or in vitro data. Dosages necessary to achieve the MEC will depend on individual characteristics and route of administration. However, HPLC assays or bioassays can be used to determine plasma concentrations. Dosage intervals can also be determined using MEC value. Compositions should be administered using a regimen which maintains plasma levels above the MEC for 10-90% of the time, preferably between 30-90% and most preferably between 50-90%. In cases of local administration or selective uptake, the effective local concentration of the drug may not be related to plasma concentration” (see [0150]). “It should be noted that the attending physician would know how to and when to terminate, interrupt or adjust administration due to toxicity or organ dysfunctions. Conversely, the attending physician would also know to adjust treatment to higher levels if the clinical response were not adequate (precluding toxicity). The magnitude of an administrated dose in the management of the disorder of interest will vary with the severity of the disease or condition to be treated and to the route of administration. The severity of the disease or condition may, for example, be evaluated, in part, by standard prognostic evaluation methods. Further, the dose and perhaps dose frequency will also vary according to the age, body weight and response of the individual patient. A program comparable to that discussed above may be used in veterinary medicine” (see [0151]).
In other words, Huang teaches that dosing optimization is routine practice in the pharmaceutical art, and although Huang does not explicitly teaches “intermittent dosing” (according to the specification the “intermittent dosing” phase is when the amount of the dose and/or the frequency of administration of ZN-c3 to the subject is changed (see for example instant specification [0019] and [0040])), Huang clearly teaches that the dose and perhaps dose frequency will also vary according to the age, body weight and response of the individual patient (see above) which is equivalent to “intermittent dosing” .Further “intermittent dosing” is routine practice in the pharmaceutical art .
All this will result in the practice of claim 1-2 with a reasonable expectation of success.
For claim 3, Huang teaches the oral administration of ZN-c3 (see [0129]), thus resulting in the practice of claim 3 with a reasonable expectation of success.
For claims 5, 11-13 and 15-17, ZENTALIS teaches the administration of 25 mg per day up to 450 mg per day of ZN-c3, which overlaps with the instantly claimed ranges (200 mg per day to 350 mg per day in claim 5, 200 mg per day in claim 11, more than 300 mg per day in claim 12, 300 mg to 350 mg per day in claim 13, 200 mg once daily in claim 15, more than 300 mg once daily in claim 16, and 300 mg to 350 mg per day in claim 17).
MPEP 2144.05 states: 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). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
"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).
All this will result in the practice of claim 5, 11-13 and 15-17 with a reasonable expectation of success.
For claims 6, 8-10 and 26, Huang teaches that: “the desired dose may conveniently be presented in a single dose or as divided doses administered at appropriate intervals, for example, as two, three, four or more sub-doses per day. The sub-doses may be further divided into a number of discrete loosely spaced administrations” (see [0148]). “As will be readily apparent to one skilled in the art, the useful in vivo dosage to be administered and the particular mode of administration will vary depending upon the age, weight, the severity of the affliction, the mammalian species treated, the particular compounds employed and the specific use for which these compounds are employed. The determination of effective dosage levels, that is the dosage levels necessary to achieve the desired result, can be accomplished by one skilled in the art using routine methods, for example, human clinical trials, in vivo studies and in vitro studies” (see [0149]).
Further, dose optimization is routine practice in the pharmaceutical art.
All this will result in the practice of claims 6, 8-10 and 26 with a reasonable expectation of success.
For claims 19-20, Huang further teaches that the administration can consist in two doses per day (see [0148]) and the dose can be between 1 to 500 mg which overlaps with the instantly claimed dosages of 100 mg twice a day (claim 19) and more than 150 mg twice a day (claim 20).
MPEP 2144.05 states: 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). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
"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).
All this will result in the practice of claims 19-20 with a reasonable expectation of success.
For claim 23, ZENTALIS teaches that the treatment is effective for patients who are refractory to standard therapy or who have exhausted available treatment options, thus resulting in the practice of claim 23 with a reasonable expectation of success.
2) Claim(s) 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over ZENTALIS press release (April 12, 2021, cited by Applicant) in view of Huang et. al. (WO 2019/173082, 09/12/2019, cited by Applicant) as applied to claims 1-3, 5-6, 8-13, 15-17, 19-20, 23 and 26 above, further in view of Salem et. al. (US 2020/0390717).
ZENTALIS in view of Huang teach all the limitations of claim 25, except for the co-administration of paclitaxel. However, Salem teaches that paclitaxel is effective in treating USC (see [0003]).
Before the effective filing date of the claimed invention, it would have been prima facie obvious for a person of ordinary skill in the art to treat USC combining two compositions (ZN-c3 and paclitaxel) each of which is taught by the prior art to be useful for the same purpose (treating USC), in order to form a third composition to be used for the very same purpose. The idea of combining them flows logically from their having been individually taught in the prior art (see MPEP 2144.06). In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See also: In re Diamond, 360 F.2d 214, 53 C.C.P.A. 1172, 149 U.S.P.Q. 562 (C.C.P.A. 1966).
All this would result in the practice of claim 25 with a reasonable expectation of success.
Claim Rejections - 35 USC § 103 (New Rejection not Necessitated by Amendment).
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
1) Claim(s) 1-3, 5-6, 8-13, 15-17, 19-20, 23 and 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Clinical Trial NCT0481418 (March 22, 2021, cited by Applicant) in view of Huang et. al. (WO 2019/173082, 09/12/2019, cited by Applicant).
For claim 1-2, NCT0481418 teaches a method of treating Uterine Serous Carcinoma (USC) comprising the administration of a therapeutically effective amount of ZN-c3 ((R)-2-allyl-1-(7-ethyl-7-hydroxy-6,7-dihydro-5H- cyclopenta-[b]-pyridin-2-yl)-6-(4-methylpiperazin-1-yl)-phenyl)-amino)-1,2-dihydro-3H pyrazolo-[3,4-d]-pyrimidin-3-one, AZENOSERTIB) to a subject in need thereof.
NCT0481418 does not teach that the dosing regimen comprises intermittent dosing phase. However, Huang teaches that substituted 1,2-dihydro-3H-pyrazolo-[3,4-D]-pyrimidin-3-ones are effective in treating all different types of cancers including uterus body cancers, wherein the 1,2-dihydro-3H-pyrazolo-[3,4-D]-pyrimidin-3-one can be ZN-c3 (see abstract, paragraph [0138] and example 9B on page 70).
Huang further teaches:
“The desired dose may conveniently be presented in a single dose or as
divided doses administered at appropriate intervals, for example, as two, three, four or more sub-doses per day. The sub-dose itself may be further divided, e.g., into a number of discrete loosely spaced administrations” (see [0148]). “As will be readily apparent to one skilled in the art, the useful in vivo dosage to be administered and the particular mode of administration will vary depending upon the age, weight, the severity of the affliction, the mammalian species treated, the particular compounds employed and the specific use for which these compounds are employed. The determination of effective dosage levels, that is the dosage levels necessary to achieve the desired result, can be accomplished by one skilled in the art using routine methods, for example, human clinical trials, in vivo studies and in vitro studies” (see [0149]). ”Dosage amount and interval may be adjusted individually to provide plasma levels of the active moiety which are sufficient to maintain the modulating effects, or minimal effective concentration (MEC). The MEC will vary for each compound but can be estimated from in vivo and/or in vitro data. Dosages necessary to achieve the MEC will depend on individual characteristics and route of administration. However, HPLC assays or bioassays can be used to determine plasma concentrations. Dosage intervals can also be determined using MEC value. Compositions should be administered using a regimen which maintains plasma levels above the MEC for 10-90% of the time, preferably between 30-90% and most preferably between 50-90%. In cases of local administration or selective uptake, the effective local concentration of the drug may not be related to plasma concentration” (see [0150]). “It should be noted that the attending physician would know how to and when to terminate, interrupt or adjust administration due to toxicity or organ dysfunctions. Conversely, the attending physician would also know to adjust treatment to higher levels if the clinical response were not adequate (precluding toxicity). The magnitude of an administrated dose in the management of the disorder of interest will vary with the severity of the disease or condition to be treated and to the route of administration. The severity of the disease or condition may, for example, be evaluated, in part, by standard prognostic evaluation methods. Further, the dose and perhaps dose frequency will also vary according to the age, body weight and response of the individual patient. A program comparable to that discussed above may be used in veterinary medicine” (see [0151]).
In other words, Huang teaches that dosing optimization is routine practice in the pharmaceutical art, and although Huang does not explicitly teaches “intermittent dosing” (according to the specification the “intermittent dosing” phase is when the amount of the dose and/or the frequency of administration of ZN-c3 to the subject is changed (see for example instant specification [0019] and [0040])), Huang clearly teaches that the dose and perhaps dose frequency will also vary according to the age, body weight and response of the individual patient (see above) which is equivalent to “intermittent dosing” .Further “intermittent dosing” is routine practice in the pharmaceutical art .
All this will result in the practice of claim 1-2 with a reasonable expectation of success.
For claim 3, Huang teaches the oral administration of ZN-c3 (see [0129]), thus resulting in the practice of claim 3 with a reasonable expectation of success.
For claims 5, 11-13 and 15-17, Huang teaches the administration of 1 mg per day up to 500 mg per day of ZN-c3 (see [0147]), which overlaps with the instantly claimed ranges (200 mg per day to 350 mg per day in claim 5, 200 mg per day in claim 11, more than 300 mg per day in claim 12, 300 mg to 350 mg per day in claim 13, 200 mg once daily in claim 15, more than 300 mg once daily in claim 16, and 300 mg to 350 mg per day in claim 17).
MPEP 2144.05 states: 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). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
"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).
All this will result in the practice of claim 5, 11-13 and 15-17 with a reasonable expectation of success.
For claims 6, 8-10 and 26, Huang teaches that: “the desired dose may conveniently be presented in a single dose or as divided doses administered at appropriate intervals, for example, as two, three, four or more sub-doses per day. The sub-doses may be further divided into a number of discrete loosely spaced administrations” (see [0148]). “As will be readily apparent to one skilled in the art, the useful in vivo dosage to be administered and the particular mode of administration will vary depending upon the age, weight, the severity of the affliction, the mammalian species treated, the particular compounds employed and the specific use for which these compounds are employed. The determination of effective dosage levels, that is the dosage levels necessary to achieve the desired result, can be accomplished by one skilled in the art using routine methods, for example, human clinical trials, in vivo studies and in vitro studies” (see [0149]).
Further, dose optimization is routine practice in the pharmaceutical art.
All this will result in the practice of claims 6, 8-10 and 26 with a reasonable expectation of success.
For claims 19-20, Huang further teaches that the administration can consist in two doses per day (see [0148]) and the dose can be between 1 to 500 mg which overlaps with the instantly claimed dosages of 100 mg twice a day (claim 19) and more than 150 mg twice a day (claim 20).
MPEP 2144.05 states: 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). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
"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).
All this will result in the practice of claims 19-20 with a reasonable expectation of success.
For claim 23, Huang teaches that the treatment is effective for patients who are resistant to other treatments (see [0139]), thus resulting in the practice of claim 23 with a reasonable expectation of success.
2) Claim(s) 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Clinical Trial NCT0481418 (March 22, 2021, cited by Applicant) in view of Huang et. al. (WO 2019/173082, 09/12/2019, cited by Applicant) as applied to claims 1-3, 5-6, 8-13, 15-17, 19-20, 23 and 26 above, further in view of Salem et. al. (US 2020/0390717).
Clinical Trial NCT0481418 in view of Huang teach all the limitations of claim 25, except for the co-administration of paclitaxel. However, Salem teaches that paclitaxel is effective in treating USC (see [0003]).
Before the effective filing date of the claimed invention, it would have been prima facie obvious for a person of ordinary skill in the art to treat USC combining two compositions (ZN-c3 and paclitaxel) each of which is taught by the prior art to be useful for the same purpose (treating USC), in order to form a third composition to be used for the very same purpose. The idea of combining them flows logically from their having been individually taught in the prior art (see MPEP 2144.06). In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See also: In re Diamond, 360 F.2d 214, 53 C.C.P.A. 1172, 149 U.S.P.Q. 562 (C.C.P.A. 1966).
All this would result in the practice of claim 25 with a reasonable expectation of success.
Claim Rejections - 35 USC § 103 (New Rejection not Necessitated by Amendment).
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
1) Claim(s) 1-3, 5-6, 8-13, 15-17, 19-20, 23 and 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu et. al. (Journal of Clinical Oncology (March 11, 2021) 39:1531-1539, cited by Applicant) in view of Huang et. al. (WO 2019/173082, 09/12/2019, cited by Applicant).
For claim 1-2, Liu teaches a method of treating Uterine Serous Carcinoma (USC) comprising the administration of a therapeutically effective amount of the WEE1 kinase inhibitor Adavosertib (AZD1775, MK-1775):
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(see abstract and entire document).
Liu does not teach the administration of:ZN-c3 ((R)-2-allyl-1-(7-ethyl-7-hydroxy-6,7-dihydro-5H- cyclopenta-[b]-pyridin-2-yl)-6-(4-methylpiperazin-1-yl)-phenyl)-amino)-1,2-dihydro-3H pyrazolo-[3,4-d]-pyrimidin-3-one, AZENOSERTIB):
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However, Huang teaches that substituted 1,2-dihydro-3H-pyrazolo-[3,4-D]-pyrimidin-3-ones are WEE1 inhibitors and are effective in treating all different types of cancers including uterus body cancers, wherein the 1,2-dihydro-3H-pyrazolo-[3,4-D]-pyrimidin-3-one can be ZN-c3 (see abstract, paragraphs [0135] and [0138] and example 9B on page 70).
Before the effective filing date of the claimed invention, it would have been prima facie obvious for a person of ordinary skill in the art to substitute one functional equivalence (any WEE1 Kinase inhibitor like Adavosertib) for another WEE1 kinase inhibitor (ZN-c3) with an expectation of success, since the prior art establishes that both function in similar manner. The skilled in the art will be further motivated to replace Adavosertib with ZN-c3 due to the extremely close structural characteristics (see above), and since both seem to be effective in treating cancers of the uterus.
Liu further teaches the treatment of USC comprising the administration of 300 mg of Adavosertib once daily through days 1 through 5 and 8 through 12 (see abstract), which according to the instant specification qualifies as an intermittent dosing (according to the specification the “intermittent dosing” phase is when the amount of the dose and/or the frequency of administration of ZN-c3 to the subject is changed (see for example instant specification [0019] and [0040])),
Huang further teaches:
“The desired dose may conveniently be presented in a single dose or as
divided doses administered at appropriate intervals, for example, as two, three, four or more sub-doses per day. The sub-dose itself may be further divided, e.g., into a number of discrete loosely spaced administrations” (see [0148]). “As will be readily apparent to one skilled in the art, the useful in vivo dosage to be administered and the particular mode of administration will vary depending upon the age, weight, the severity of the affliction, the mammalian species treated, the particular compounds employed and the specific use for which these compounds are employed. The determination of effective dosage levels, that is the dosage levels necessary to achieve the desired result, can be accomplished by one skilled in the art using routine methods, for example, human clinical trials, in vivo studies and in vitro studies” (see [0149]). ”Dosage amount and interval may be adjusted individually to provide plasma levels of the active moiety which are sufficient to maintain the modulating effects, or minimal effective concentration (MEC). The MEC will vary for each compound but can be estimated from in vivo and/or in vitro data. Dosages necessary to achieve the MEC will depend on individual characteristics and route of administration. However, HPLC assays or bioassays can be used to determine plasma concentrations. Dosage intervals can also be determined using MEC value. Compositions should be administered using a regimen which maintains plasma levels above the MEC for 10-90% of the time, preferably between 30-90% and most preferably between 50-90%. In cases of local administration or selective uptake, the effective local concentration of the drug may not be related to plasma concentration” (see [0150]). “It should be noted that the attending physician would know how to and when to terminate, interrupt or adjust administration due to toxicity or organ dysfunctions. Conversely, the attending physician would also know to adjust treatment to higher levels if the clinical response were not adequate (precluding toxicity). The magnitude of an administrated dose in the management of the disorder of interest will vary with the severity of the disease or condition to be treated and to the route of administration. The severity of the disease or condition may, for example, be evaluated, in part, by standard prognostic evaluation methods. Further, the dose and perhaps dose frequency will also vary according to the age, body weight and response of the individual patient. A program comparable to that discussed above may be used in veterinary medicine” (see [0151]).
In other words, Huang teaches that dosing optimization is routine practice in the pharmaceutical art, and although Huang does not explicitly teaches “intermittent dosing” (according to the specification the “intermittent dosing” phase is when the amount of the dose and/or the frequency of administration of ZN-c3 to the subject is changed (see for example instant specification [0019] and [0040])), Huang clearly teaches that the dose and perhaps dose frequency will also vary according to the age, body weight and response of the individual patient (see above) which is equivalent to “intermittent dosing” .Further “intermittent dosing” is routine practice in the pharmaceutical art .
All this will result in the practice of claim 1-2 with a reasonable expectation of success.
For claim 3, Liu teaches the oral administration of Adavosertib (see abstract) and Huang teaches the oral administration of ZN-c3 (see [0129]), thus resulting in the practice of claim 3 with a reasonable expectation of success.
For claims 5, 11-13 and 15-17,Huang teaches the administration of 1 mg per day up to 500 mg per day of ZN-c3 (see [0147]), which overlaps with the instantly claimed ranges (200 mg per day to 350 mg per day in claim 5, 200 mg per day in claim 11, more than 300 mg per day in claim 12, 300 mg to 350 mg per day in claim 13, 200 mg once daily in claim 15, more than 300 mg once daily in claim 16, and 300 mg to 350 mg per day in claim 17).
MPEP 2144.05 states: 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). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
"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).
All this will result in the practice of claim 5, 11-13 and 15-17 with a reasonable expectation of success.
For claims 6, 8-10 and 26, Huang teaches that: “the desired dose may conveniently be presented in a single dose or as divided doses administered at appropriate intervals, for example, as two, three, four or more sub-doses per day. The sub-doses may be further divided into a number of discrete loosely spaced administrations” (see [0148]). “As will be readily apparent to one skilled in the art, the useful in vivo dosage to be administered and the particular mode of administration will vary depending upon the age, weight, the severity of the affliction, the mammalian species treated, the particular compounds employed and the specific use for which these compounds are employed. The determination of effective dosage levels, that is the dosage levels necessary to achieve the desired result, can be accomplished by one skilled in the art using routine methods, for example, human clinical trials, in vivo studies and in vitro studies” (see [0149]).
Further, dose optimization is routine practice in the pharmaceutical art.
All this will result in the practice of claims 6, 8-10 and 26 with a reasonable expectation of success.
For claims 19-20, Huang further teaches that the administration can consist in two doses per day (see [0148]) and the dose can be between 1 to 500 mg which overlaps with the instantly claimed dosages of 100 mg twice a day (claim 19) and more than 150 mg twice a day (claim 20).
MPEP 2144.05 states: 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). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
"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).
All this will result in the practice of claims 19-20 with a reasonable expectation of success.
For claim 23, Huang teaches that the treatment is effective for patients who are resistant to other treatments (see [0139]), thus resulting in the practice of claim 23 with a reasonable expectation of success.
2) Claim(s) 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu et. al. (Journal of Clinical Oncology (March 11, 2021) 39:1531-1539, cited by Applicant) in view of Huang et. al. (WO 2019/173082, 09/12/2019, cited by Applicant) as applied to claims 1-3, 5-6, 8-13, 15-17, 19-20, 23 and 26 above, further in view of Salem et. al. (US 2020/0390717).
Liu et. al. in view of Huang teach all the limitations of claim 25, except for the co-administration of paclitaxel. However, Salem teaches that paclitaxel is effective in treating USC (see [0003]).
Before the effective filing date of the claimed invention, it would have been prima facie obvious for a person of ordinary skill in the art to treat USC combining two compositions (ZN-c3 and paclitaxel) each of which is taught by the prior art to be useful for the same purpose (treating USC), in order to form a third composition to be used for the very same purpose. The idea of combining them flows logically from their having been individually taught in the prior art (see MPEP 2144.06). In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See also: In re Diamond, 360 F.2d 214, 53 C.C.P.A. 1172, 149 U.S.P.Q. 562 (C.C.P.A. 1966).
All this would result in the practice of claim 25 with a reasonable expectation of success.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
1) Claims 1-3, 5-6, 8-13, 15-17, 19-20, 23 and 25-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 24 of copending Application No. 17/998,561 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant application and the co-pending application teach a method of treating USC comprising the administration of a composition comprising ZN-c3.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
2) Claims 1-3, 5-6, 8-13, 15-17, 19-20, 23 and 25-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4 and 11 of copending Application No. 18/634,055 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant application and the co-pending application teach a method of treating USC comprising the administration of a composition comprising ZN-c3.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
3) Claims 1-3, 5-6, 8-13, 15-17, 19-20, 23 and 25-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 30 and 46 of copending Application No. 19/045,327 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant application and the co-pending application teach a method of treating USC comprising the administration of a composition comprising ZN-c3.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
4) Claims 1-3, 5-6, 8-13, 15-17, 19-20, 23 and 25-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 29 of copending Application No. 19/201,446(reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant application and the co-pending application teach a method of treating USC comprising the administration of a composition comprising ZN-c3.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
5) Claims 1-3, 5-6, 8-13, 15-17, 19-20, 23 and 25-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 31 of copending Application No. 19/201,378 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant application and the co-pending application teach a method of treating USC comprising the administration of a composition comprising ZN-c3.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
6) Claims 1-3, 5-6, 8-13, 15-17, 19-20, 23 and 25-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 36 of copending Application No. 19/404,321 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant application and the co-pending application teach a method of treating USC comprising the administration of a composition comprising ZN-c3.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
7) Claims 1-3, 5-6, 8-13, 15-17, 19-20, 23 and 25-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 39 of copending Application No. 18/004,628 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant application and the co-pending application teach a method of treating USC comprising the administration of a composition comprising ZN-c3.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCOS L SZNAIDMAN whose telephone number is (571)270-3498. The examiner can normally be reached Flexing M-F 7 AM-7 PM.
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/MARCOS L SZNAIDMAN/
Primary Examiner, Art Unit 1628
September 14, 2026.
Prosecution Insights