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
The present Application, filed February 22, 2021, is a Continuation of U.S. Patent Application No. 16/178419 (now U.S. Patent No. 10,925,878), filed November 1, 2018, which is a Continuation of U.S. Patent Application No. 16/112,362 (now U.S. Patent No. 10,434,104), filed August 24, 2018, which is a Continuation of U.S. Patent Application No. 15/387,083 (now U.S. Patent No. 10,076,523), filed December 21, 2016, which is a Continuation of U.S. Patent Application No. 14/214,048 (now U.S. Patent No. 9,527,857), filed March 14, 2014, which claims the benefit of U.S. Provisional Patent Application Nos. 61/949,786, 61/911,354, 61/861,374, and 61/798,772, filed March 7, 2014, December 3, 2013, August 1, 2013, and March 15, 2013, respectively.
Status of the Claims
Claims 17-38 remain currently pending.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on February 12, 2026 are acknowledged.
Response to Arguments
Rejections for nonstatutory double patenting:
In Applicant’s Remarks of February 12, 2026, Applicant notes that U.S. Application No. 17/854,755 has been abandoned. Accordingly, the rejections of the instant claims for nonstatutory double patenting over the claims of this now-abandoned application are withdrawn.
Applicant further argues that the instant claims are not obvious variations of the claimed subject matter of the remaining reference patents and applications because none of the reference applications recite daily administration of lerociclib for at least 24 consecutive days and it would have been non-obvious to administer lerociclib for this duration.
Applicant first asserts that one would not have utilized the teachings of the cited secondary reference, Baker, to determine a dosing regimen for lerociclib, because Baker teaches dosing of palbociclib, a related but distinct compound (pg. 6 of Applicant’s Response, first full paragraph). It is noted, however, that Baker is not cited for teaching the particulars of a dosing regimen, but rather for providing the broad outlines of a dosing regimen and establishing factors like administration frequency and duration as result effective variables.
Applicant further argues that, while Baker teaches administration of palbociclib for 21 days, the evidence in Baker would have discourage one from extending the administration duration beyond this; because the clinical trial that Baker references showed neutropenia increased with increasing administration duration, platelet and neutrophil count decreased during the administration phase of the cycle, and these levels recovered during the “off-drug” phase of the cycle (paragraph spanning the bottom of pg. 6 to the top of pg. 7 of Applicant’s Remarks). Applicant contends that on this basis, the skilled person would have been dissuaded from extending the administration duration beyond 21 days (first two full paragraphs of pg. 7 of Applicant’s Remarks). This argument has been fully considered, but is not found persuasive.
As a first matter, as noted, neither Baker, nor the underlying study, was cited to establish a specific dosing regimen for lerociclib, but to establish the general outline and that factors like administration duration and frequency are result-effective variables. It is well established that where the general outlines of an invention are known in the art, variations or optimizations of these variables is routine work that does not confer patentability. See, for example, In re Aller, 220 F.2d 454 (CCPA 1955) and In re Peterson, 315 F.3d 1325 (Fed. Cir. 2003). This is particularly so where the is no evidence of criticality and, in the present case, there is no indication of criticality or even notable significance to the 24-day or 28-day administration durations.
Furthermore, the data shown in the Flaherty reference that Applicant cites (Phase I, Dose-Escalation Trial of the Oral Cyclin-Dependent Kinase 4/6 Inhibitor PD 0332991, Administered Using a 21-Day Schedule in Patients with Advanced Cancer, Clin. Canc. Res., 18, pgs. 568-576 (2012) by Flaherty et al.) does not appear to provide any particular reason why 21 days of administration should be a cutoff, or longest desirable duration. As shown, for example, in Supplementary Figure 2, these results merely indicate that platelet and neutrophil counts decrease while the drug is administered and recover when administration is discontinued, which is unsurprising. The only reason there is a nadir at 21 days is because administration was discontinued after 21 days, and the nadir would presumably have been at 24 or 28 days if that had been the duration of administration. In short, Flaherty does not support a finding that 21 days in particular should be the maximum duration of continuous administration of palbociclib, much less of lerociclib.
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Above: Supplementary Figure 2 of Flaherty, showing the response of neutrophil and platelet counts to a cycle of administration and discontinuation of palbociclib.
Finally, Applicant asserts that the Office Action’s reference to obviousness of adjacent ranges, and citation of Titanium Metals Corp. of America v. Banner is inapt because modest adjustment to a drug administration schedule can materially alter outcomes. However, as noted above, there is no evidence of criticality nor even of particular importance to the 21 day administration duration of Baker, nor of the 24 or 28 day administration duration of the instant claims. While Applicant asserts that Flaherty supports a divergence between (i) the asserted obviousness of a dose regimen compared to a highly similar prior art regimen and (ii) the obviousness of claimed metal concentrations in an alloy over similar prior art concentrations, it is unclear how Flaherty supports this. It is noted that Flaherty modulates drug dose while utilizing the same administration duration for all subjects. As such, Flaherty does not appear to support the proposition that that the effects of changing the administration duration for a CDK4/6 inhibitor would be substantially less predictable than the effects of changing metal composition of an alloy. Furthermore, it is reiterated that the nonobviousness of an altered value in a result-effective variable (such as administration duration in a dosing regimen) is difficult to establish when there is no evidence of criticality or even of particular significance to the claimed value (24 or 28 days of continuous administration, in the present case).
For the aforementioned reasons, the rejections, as modified, are maintained.
Double Patenting – Rejections Modified in View of Arguments, But Substantially Maintained
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.
Claims 17-38 are rejected for nonstatutory double patenting over the ’352 patent and Baker:
Claims 17-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-51 of U.S. Patent No. 11,529,352 (hereinafter, “the ’352 patent”), in view of the non-patent publication, CDK4: A Key Player in the Cell Cycle, Development, and Cancer, Genes Cancer, 3, pgs. 658-669 (2012) by Baker et al. (hereinafter, “Baker”).
Claims 17-38 are rejected for nonstatutory double patenting over the ’222 patent and Baker:
Claims 17-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. 11,364,222 (hereinafter, “the ’222 patent”), in view of Baker.
Claims 17-38 are rejected for nonstatutory double patenting over the ’779 patent and Baker:
Claims 17-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-52 of U.S. Patent No. 11,357,779 (hereinafter, “the ’779 patent”), in view of Baker.
Claims 17-38 are rejected for nonstatutory double patenting over the ’711 patent and Baker:
Claims 17-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10,709,711 (hereinafter, “the ’711 patent”), in view of Baker.
Claims 17-38 are rejected for nonstatutory double patenting over the ’193 patent and Baker:
Claims 17-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,261,193 (hereinafter, “the ’193 patent”), in view of Baker.
Claims 17-38 are rejected for nonstatutory double patenting over the ’821 patent and Baker:
Claims 17-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11,395,821 (hereinafter, “the ’821 patent”), in view of Baker.
Claims 17-38 are rejected for nonstatutory double patenting over the ’547 patent and Baker:
Claims 17-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 10,413,547 (hereinafter, “the ’547 patent”), in view of Baker.
Claims 17-38 are rejected for nonstatutory double patenting over the ’306 patent and Baker:
Claims 17-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,090,306 (hereinafter, “the ’306 patent”), in view of Baker.
Claims 17-38 are rejected for nonstatutory double patenting over the ’969 patent and Baker:
Claims 17-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 10,231,969 (hereinafter, “the ’969 patent”), in view of Baker.
Claims 17-38 are rejected for nonstatutory double patenting over the ’295 patent and Baker:
Claims 17-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,446,295 (hereinafter, “the ’295 patent”), in view of Baker.
Claims 17-38 are rejected for nonstatutory double patenting over the ’530 patent and Baker:
Claims 17-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-50 of U.S. Patent No. 9,487,530 (hereinafter, “the ’530 patent”), in view of Baker.
Claims 17-38 are rejected for nonstatutory double patenting over the ’857 patent and Baker:
Claims 17-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-74 of U.S. Patent No. 9,527,857 (hereinafter, “the ’857 patent”), in view of Baker.
Claims 17-38 are rejected for nonstatutory double patenting over the ’523 patent and Baker:
Claims 17-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-15 of U.S. Patent No. 10,076,523 (hereinafter, “the ’523 patent”), in view of Baker.
Claims 17-38 are rejected for nonstatutory double patenting over the ’104 patent and Baker:
Claims 17-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-10 of U.S. Patent No. 10,434,104 (hereinafter, “the ’104 patent”), in view of Baker.
Claims 17-38 are rejected for nonstatutory double patenting over the ’148 patent and Baker:
Claims 17-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-16 of U.S. Patent No. 11,654,148 (hereinafter, “the ’148 patent”), in view of Baker.
Claims 17-38 are rejected for nonstatutory double patenting over the ’697 patent and Baker:
Claims 17-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-18 of U.S. Patent No. 12,364,697 (hereinafter, “the ’697 patent”), in view of Baker.
Although the claims at issue are not identical, they are not patentably distinct from each other because the scope of the instant claims substantially overlaps with the scope of the claims of each of the reference applications, as modified by the known features of Baker.
Instant claim 17 recites a method for treating retinoblastoma (Rb )-positive uterine cancer in a human comprising administering to the human an effective amount of a selective cyclin dependent kinase 4/6 (CDK4/6) inhibitor compound of structure:
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(i.e. lerociclib) or a pharmaceutically acceptable salt thereof, wherein the CDK4/6 inhibitor is administered to the human at least once a day for 24 or more continuous days. Claim 28 recites an equivalent method of treating an Rb-positive endometrial cancer. Dependent claims 24-27 and 35-38 recite that an additional chemotherapeutic agent is also administered, and recite various alternatives for the additional agent. Other dependent claims recite more specific features of the administration, such as longer durations of continuous days, number of times per day, or route of administration (e.g. oral administration).
All of the reference patents recite, at minimum, lerociclib. For example, the ’193 patent recites a crystalline polymorph of lerociclib, a process for making it, and a pharmaceutical composition having the polymorph.
All of the reference patents recite a method (or in a few instances, a dosing regimen) for treating a cancer, particularly a Rb-positive cancer, the method comprising administering an effective amount of lerociclib to a human in need thereof. Some of the references (e.g. the ’857 patent) explicitly recite a RB-positive cancer, other recite cancers that would fall within the definition of an Rb-positive cancer as given in the instant specification.
For example, claim 1 of the ’352 patent recites a method of treating a human having cancer, the method comprising, inter alia, administering to the human an effective amount of lerociclib. Claim 1 of the ’352 patent further recites administering to the human an effective amount of a chemotherapeutic agent (comparable to instant claims 24-27 and 35-38).
Similarly, the ’222 patent recites a method of treating an estrogen-related cancer in a human comprising administering a selective estrogen receptor downregulator in combination with a CDK4/6 inhibitor which can be lerociclib.
The reference patents generally do not recite administration for 24 or more continuous days, but such administration would have been an obvious variation because daily administration of CDK4/6 inhibitors for the treatment of cancer was well-known in the art, as taught for example by Baker.
Baker teaches a review of the role of CDK4 in the cell cycle and in cancer (Abstract). Baker teaches a phase I trial of oral PD-0332991, a selective CDK4/6 inhibitor (pg. 665, right column, first full paragraph), noting that the compound was administered daily for 21 days in 28 day cycles. While this 21 continuous days of administration is just outside the range recited in instant claims 17 and 28 (and instant claims 19-20 and 30-31), a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783 (Fed. Cir. 1985). See also MPEP 2144.05(I) and cases cited therein. Furthermore, Baker recognizes administration duration as a result-effective variable, and optimization of such a variable would have been routine.
Similarly, whether the CDK4/6 inhibitor is administered once or twice daily would have been a matter of routine optimization, particularly given that Baker recognizes administration frequency as a result-effective variable. Furthermore, while most of the reference patents explicitly recite administration of an additional chemotherapeutic agent along with the lerociclib, Baker further teaches that combination therapy of a CDK4/6 inhibitor (e.g. PD-0332991) with an additional chemotherapeutic agent (e.g. letrozole) has given encouraging results. Such combination therapy with the CDK4/6 inhibitor of the instant claims, lerociclib, would have been obvious over any of the reference patents that do not explicitly recite it, in view of Baker.
Provisional rejections for nonstatutory double patenting:
Claims 17-38 are provisionally rejected for nonstatutory double patenting over the ’052 application and Baker:
Claims 17-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-23 of copending U.S. Patent Application No. 17/718,052 (hereinafter, “the ’052 application”), in view of Baker. The ’052 application corresponds to U.S. Patent Application Publication No. 2022/0241275, cited in the form PTOL-892, attached to this Action.
Although the claims at issue are not identical, they are not patentably distinct from each other because the scope of the instant claims substantially overlaps with the scope of the claims of each of the reference applications, as modified by the known features of Baker.
The ’052 application recites a method of treating a human with non-small cell lung cancer comprising administering lerociclib along with an effective amount of an epidermal growth factor receptor tyrosine kinase inhibitor. The ’052 application recites a method of treating a human host with a cancer having a dysregulated FGFR signaling pathway, the method comprising administering lerociclib and an effective amount of a selective fibroblast growth factor receptor tyrosine kinase inhibitor. Baker is applied as above.
This is a provisional rejection.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER K SHOWALTER whose telephone number is (571)270-0610. The examiner can normally be reached M-F 9:00 am to 5:00 pm, eastern time.
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/ALEXANDER K. SHOWALTER/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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