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 .
Current Status
This action is responsive to the amended claims of 10/21/2025. Claims 1-23 are pending. Claims 1-12 and 14 are withdrawn. Claims 13 and 15-23 have been examined on the merits.
This action is made second non-final to provide Applicant an opportunity to reply to art that was missed in the first round of examination.
Election/Restrictions
The showing of unexpected results in the remarks of 10/21/2025 has overcome the previous 103 rejection. A search for the claimed compound lerociclib and the elected FGFR-TKI erdafitinib only returned two documents (WO 2019/006393 & WO 2019136451) published within the grace period and having shared inventor/assignee. The documents regard treatment of urothelial cancer – thus, the species of cancer is expanded to urothelial cancer.
The Markush search has also been extended to the following species: H3B-6527 and hepatocellular carcinoma.
The species erdafitinib and urothelial cancer read on claims 13 and 15-18.
The extended species H3B-6527 and hepatocellular carcinoma read on claims 19-23.
Claims 1-12 and 14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/01/2025.
Priority
The effective filing date remains 10/09/2019.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 10/21/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Response to Arguments
Examiner acknowledges receipt of and has reviewed the remarks and amendments of 10/21/2025; no new matter is found.
The objections to claims 4, 5, 21, and 22 are all withdrawn because Applicant has amended the claims in line with Examiner’s suggestions.
The 103 rejection of claims 7-10 and 12 over STRUM, DIENSTMANN, and NISHINA is withdrawn in view of Applicant’s arguments. Applicant argues that the data shown in the specification, in particular Fig. 1B, shows an enhanced anticancer inhibitory effect when the instantly claimed CDK 4/6 inhibitor (lerociclib) is combined with an FGFR inhibitor that is erdafitinib in an FGFR2 aberrant cell line of gastric cancer. Applicant argues the combination of lerociclib with an FGFR inhibitor is synergistic and more efficacious and that the prior art references do not teach or suggest this enhanced anti-cancer inhibitory effect.
Examiner notes the prior art references do not teach the combination of lerociclib with an FGFR inhibitor. The prior art teaches each component (lerociclib and erdafitinib), separately, has an anticancer inhibitory effect. However, as shown by the Applicant’s data (e.g., Fig. 1B), the anticancer inhibitory effect is superior in the claimed combination. Thus, the enhanced anticancer inhibition of the combination treatment is understood as a superiority of a property shared with the prior art; this is evidence of nonobviousness (see MPEP 716.02(a)).
Further, Examiner notes Figures 1A and 1C show the same evidence for the combination of lerociclib with an FGFR inhibitor (erdafitinib) in an exemplary FGFR1 aberrant cancer and FGFR3 aberrant cancer, respectively. The evidence of Figs. 1A-C is understood to be commensurate in scope with the claims 1-18. The claims 1-18 are drawn to administration of one specific CDK 4/6 inhibitor, lerociclib, in combination with an FGFR inhibitor (FGFR-TKI) to a human having a cancer caused by an FGFR 1, 2, or 3 aberration. The instant data reflects the claimed CDK 4/6 inhibitor, lerociclib. The instant data is exemplary of the instantly claimed FGFR inhibitors and FGFR 1, 2, or 3 aberration-characterized cancers. Since the claims are narrow in respect to the CDK 4/6 inhibitor lerociclib, the claimed FGFR inhibitors and FGFR 1, 2, or 3 aberration-characterized cancers must be considered in the context of lerociclib. Therefore, the data, showing a superiority in anticancer inhibitory activity when lerociclib is combined with an FGFR inhibitor in FGFR-aberrant cancers, is commensurate in scope with the claims.
The 103 rejection of claims 7 and 11 over STRUM, DIENSTMANN, and NISHINA further in view of SMITH is withdrawn in view of Applicant’s arguments. Applicant’s argument discussed, above, overcome the basis for this rejection (i.e., the combination of STRUM, DIENSTMANN, and NISHINA). The addition of SMITH does not rectify the deficiencies of the base references as it merely teaches a crystal salt form of the instant compound – not the instant combination treatment.
The NSDP rejections of claims 7-11 over US 11,261,193, claims 7 and 9-10 over US 9,527,857, and claims 7 and 9-11 over US 11,357,779 (¶21-23 of the previous action mailed 04/21/2025) are all withdrawn in view of Applicant’s arguments. Each of these rejections is an obviousness-type rejection and is based in the combination of references STRUM, DIENSTMANN, and NISHINA. Applicant’s argument discussed in ¶12, above, overcomes the basis for these rejections. Thus, the rejections are withdrawn.
New Rejections – Not Necessitated by Amendment
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 19-23 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 19 recites, line 2-3, “a cancer having a dysregulated fibroblast growth factor receptor (FGFR) pathway caused by an FGFR4 aberration or FGFR aberration wherein the FGFR4 aberration comprising administering”. This phrasing is unclear, in particular the portion that is underlined. It is unclear what the final “wherein” clause is attempting to claim since it appears to be incomplete (or a typo that was not meant to be part of the claim). Thus, the metes and bounds of the claim are undefined rendering the claim indefinite. Dependent claims 20-23 are similarly rejected since they do not rectify the underlying issue.
For purposes of examination, the claim is understood to be drawn to treating a cancer with an FGFR4 or FGFR aberration.
Claim 23 recites the limitation "the FGFR-TKI" in line 1-2. There is insufficient antecedent basis for this limitation in the claim. Parent claim 19 recites an FGFR inhibitor, but does not recite an FGFR-TKI. Thus, it is unclear what FGFR-TKI claim 23 is referring to in the above limitation. Therefore, the metes and bounds of the claim are undefined rendering the claim indefinite.
To overcome: Applicant could amend claim 19 to recite FGFR-TKI, such as is seen in the other independent claims 1, 7, and 13.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 23 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 23 recites “the FGFR-TKI"; however, parent claim 19 does not recite any FGFR-TKI. Thus, claim 23 recites a limitation which does not properly further limit claim 19. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 19-21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by SELVARAJ (WO 2018/039324, pub. 03/01/2018) as evidenced by CAS RN 1702259-66-2 (American Chemical Society Chemical Abstracts Service Registry No. 1702259-66-2, available 12 May 2015, pg. 1-2).
SELVARAJ teaches a method of treating hepatocellular carcinoma in a patient comprising administering to the patient a combination of N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)-5-(4-ethylpiperazin-1-yl)phenyl)acrylamide and a CDK 4/6 inhibitor or salt thereof (Pg. 33 claim 1) wherein the CDK 4/6 inhibitor is G1T-38 (Pg. 34 claim 18). SELVARAJ teaches N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)-5-(4-ethylpiperazin-1-yl)phenyl)acrylamide is an FGFR4 inhibitor with the structure
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(Pg. 1-2 final-first paragraph). SELVARAJ teaches G1T-38 has the structure:
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(Pg. 4 ¶1) which corresponds to the instant compound. Further SELVARAJ teaches hyperactive FGFR4 is implicated in hepatocellular carcinoma and leads to increased tumor growth (Pg. 1 ¶3); i.e., aberrant FGFR4. Finally, SELVARAJ teaches the patient is a human (Pg. 15 last paragraph).
Regarding claim 21, as evidenced by CAS RN 1702259-66-2, H3B-6527 is another name for the above FGFR4 inhibitor (Pg. 1 Chemical Name: Other Names).
Thus, SELVARAJ teaches the method of instant claims 19-21.
Claims 13 and 15-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by SMITH (WO 2019/006393; cited in IDS of 08/23/2022) as evidenced by KIM (Kim, Y.S. et al., BMC Urology, 2018, 18(68), 1-7).
SMITH teaches compound 2
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(Pg. 4 Line 13), i.e., the diHCl salt of the instant CDK 4/6 inhibitor. SMITH teaches the crystal Form B of compound 2 comprises XRPD peaks (Pg. 14 Lines 19-23) which correspond to those in instant claim 17. SMITH teaches an effective amount of compound 2 Form B is administered in combination with erdafitinib for the treatment of urothelial cancer (Pg. 69 lines 10-14). SMITH further teaches a method of treating cancer in a human by administering the Form B (Pg. 96 claims 13-14). KIM discloses genomic alterations in FGFR3 are well described in urothelial cancer with the most common aberrations including gene rearrangements (Pg. 1 Right col. ¶1) such as FGFR3 fusion and translocation (Pg. 6 Left col. ¶2). Thus, urothelial cancer is understood to be a cancer having dysregulated FGFR signaling caused by an FGFR3 aberration (i.e., fusion or translocation of instant claim 15). Thus, SMITH teaches the claimed method.
Claims 13 and 15-18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by BEELEN (WO 2019/136451; cited in IDS of 08/23/2022) as evidenced by KIM (Kim, Y.S. et al., BMC Urology, 2018, 18(68), 1-7).
BEELEN teaches a dosing regime for oral delivery of compound II Form B to a human once a day (Pg. 167 claim 13) for at least 24 weeks (Pg. 168 claim 24); an additional therapeutic is administered to the human (Pg. 168 claim 25) which is erdafitinib (Pg. 169 claim 38). BEELEN teaches compound II is the diHCl salt form of the instant CDK 4/6 inhibitor lerociclib (Pg. 7 Lines 8-14) and Form B thereof comprises XRPD peaks (Pg. 155 Lines 3-5) which correspond to those in instant claim 17. BEELEN teaches an embodiment wherein an effective amount of Compound II Form B is administered in combination with erdafitinib for the treatment of urothelial cancer (Pg. 93 Lines 16-22). KIM discloses genomic alterations in FGFR3 are well described in urothelial cancer with the most common aberrations including gene rearrangements (Pg. 1 Right col. ¶1) such as FGFR3 fusion and translocation (Pg. 6 Left col. ¶2). Thus, urothelial cancer is understood to be a cancer having dysregulated FGFR signaling caused by an FGFR3 aberration (i.e., fusion or translocation of instant claim 15). In view of the complete teachings of BEELEN as evidenced by KIM, the artisan would immediately envisage the claimed method.
Note, the BEELEN’s teaching of once-a-day administration for at least 24 weeks anticipates instant claim 18 since these teachings fall within the claimed ranges of ≥once a day and ≥28 consecutive days.
To expedite allowance: Applicant may consider importing the limitations of claim 14 into independent claim 13.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 13 and 15-17 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by SMITH (WO 2019/006393; effectively filed 06/29/2018; cited in IDS of 08/23/2022) as evidenced by KIM (Kim, Y.S. et al., BMC Urology, 2018, 18(68), 1-7).
SMITH teaches the instant claims 13 and 15-17 are discussed in ¶24, above. The international filing date is used as the effectively filed date, thus, no priority document is further cited.
Claims 13 and 15-18 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by BEELEN (WO 2019/136451; effectively filed 01/08/2019; cited in IDS of 08/23/2022) as evidenced by KIM (Kim, Y.S. et al., BMC Urology, 2018, 18(68), 1-7).
BEELEN teaches the instant claims 13 and 15-18 as discussed in ¶25, above. The international filing date is used as the effectively filed date, thus, no priority document is further cited.
The applied references have a common inventor (WO 2019/136451 - Strum) or possible common assignee (WO 2019/006393 – prior assignee G1 Therapeutics) 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(a)(2) 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) if the same invention is not being claimed; 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 in the reference 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.
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 (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.
Claims 19-23 are rejected under 35 U.S.C. 103 as being unpatentable over:
SELVARAJ (WO 2018/039324) as evidenced by CAS RN 1702259-66-2 (American Chemical Society Chemical Abstracts Service Registry No. 1702259-66-2, available 12 May 2015, pg. 1-2)
as applied to claims 19-21, above, further in view of:
STRUM (US 9527857, pub. 12/27/2016, cited in IDS of 08/23/2022),
ANSEL (Ansel, H.C. et al. Pharmaceutical Dosage Forms and Drug Delivery Systems, Lippincott Williams & Wilkins, 7th ed., 1999, pages 48-53), and
SMITH (WO 2019/006393, pub. 01/03/2019, effectively filed 06/29/2018, cited in IDS of 08/23/2022).
Note: SMITH is applied under both 102(a)(1) and (a)(2) date provisions; the international filing date is used as the effectively filed date.
Determining the Scope and Contents of the Prior Art:
SELVARAJ, as evidenced by CAS, teaches the method of instant claims 19-21. SELVARAJ further teaches the FGFR4 inhibitor, above, may be administered daily for 21 days or more than one month (Pg. 18 ¶1). Further the combination daily dosage may be part of a cyclic regimen lasting 14 to 21 days or longer (Pg. 18 ¶3).
STRUM teaches the compound GG:
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(Pg. 81 Table 1); i.e., compound G1T-38 of SELVARAJ. STRUM teaches the compound GG may be administered to a subject prior to, during, or after administration of another chemotherapeutic agent (Pg. 60 Col. 8 Lines 28-32). STRUM further teaches the subject is a human (Pg. 61 Col. 9 Lines 65-66). STRUM also teaches the compound may be administered once a day for 28 continuous days (Pg. 93 Col. 73 Lines 9 & 22-24). STRUM also teaches the use of compound GG allows for the elimination of an off-cycle or drug holiday (Pg. 91 Col. 69 Lines 46-48).
ANSEL teaches the safe and effective dose of a drug depends on a number of factors including characteristics of the drug, the dosage form, and a variety of patient factors (Pg. 48 Left Col. para 2) and the effective dose may be different for different patients (Pg. 48 Left Col. para 4). ANSEL further teaches the schedule of dosage or the dosage regimen is determined based on a drug’s duration of action, pharmacokinetics, and characteristics of the dosage form (Pg. 40 Right Col. para 2).
SMITH teaches a stable form of the di-HCL salt of the instant compound
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for advantageous therapeutic pharmaceutical efficacy and dosage form stability (Pg. 1 Abstract). SMITH teaches the crystalline Form B of the di-HCL salt of the instant compound characterized by an XRPD pattern having 2theta values 6.5±0.2, 9.5±0.4, 14.0±0.2, 14.4±0.2, 18.1±0.2, 19.3±0.2, 19.9±0.2, and 22.4±0.2 (Pg. 94 claim 1). SMITH further teaches cancers can be treated with the compound Form B (Pg. 22 Lines 25-29) including hepatocellular carcinoma (Pg. 28 Line 16).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
SELVARAJ does not teach the instant Form B nor the combination treatment being administered once daily for at least 28 consecutive days.
STRUM and SMITH do not teach administration of the FGFR4 inhibitor.
ANSEL does not teach the instant method of administration.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treatment of hepatocellular carcinoma and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the dosing and dosage form. Said artisan has also reviewed the problems in the art regarding dosing regimens and forms and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references SELVARAJ (evidenced by CAS), STRUM, ANSEL, and SMITH.
Regarding claims 19-21 and 22, the artisan would have been motivated to optimize the dosage regimen of the combination treatment.
MPEP 2144.05(II)(A) provides guidance about the routine optimization of prior art conditions: "Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature 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). "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.").”
Furthermore, MPEP 2144.05(I) provides guidance about overlapping ranges: “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists…Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close.”
In the instant case, SELVARAJ teaches a dose regimen of at least once daily dosing for 21 days or more (Pg. 18 ¶1-3) and STRUM teaches the instant CDK 4/6 compound is administered once a day for 28 continuous days (Pg. 93 Col. 73 Lines 9 & 22-24). These dosage regimens are considered to overlap with/approach the instantly claimed combination administration of at least once a day for at least 28 consecutive days. Since ANSEL teaches dosage regimens are based on duration of action, pharmacokinetics, and the dosage form (Pg. 40 Right Col. para 2) and the effective dosing may be different for different patients (Pg. 48 Left Col. para 4), the artisan would recognize the dosage regimen (i.e., per day & # of days) of the combination treatment as a result-effective variable, i.e., a variable that achieves a recognized result. Thus, the dosage is analogous to the “concentration or temperature” recited in the MPEP and may be optimized by routine experimentation. Therefore, the determination of the optimum or workable dosage regimen of the combination treatment would have been well within the practice of the artisan. Furthermore, absent any evidence demonstrating a patentable difference between the instant and prior art compositions and the criticality of the claimed dosage regimen, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the artisan.
Moreover, since STRUM teaches the instant CDK 4/6 compound allows for the elimination of an off-cycle or drug holiday (Pg. 91 Col. 69 Lines 46-48) and is administered once a day for 28 continuous days (Pg. 93 Col. 73 Lines 9 & 22-24), the artisan would have a reasonable expectation of success in administering the combination treatment under the instantly claimed dosage regimen.
Regarding claims 19-21 and 23, the artisan would have been motivated to replace the compound G1T-38 of SELVARAJ with the di-HCl Form B thereof to capitalize on Form B’s advantageous therapeutic pharmaceutical efficacy and dosage form stability, as recognized by SMITH (Pg. 1 Abstract). The artisan would have a reasonable expectation of success in treating the same patient of SELVARAJ with the Form B since SMITH teaches treatment of cancers, including hepatocellular carcinoma, therewith (Pg. 28 Line 16).
Claims 13 and 15-18 are rejected under 35 U.S.C. 103 as being unpatentable over:
SMITH (WO 2019/006393, pub. 01/03/2019, effectively filed 06/29/2018, cited in IDS of 08/23/2022) as evidenced by KIM (Kim, Y.S. et al., BMC Urology, 2018, 18(68), 1-7)
as applied to claims 13 and 15-17, above, further in view of:
STRUM (US 9527857, pub. 12/27/2016, cited in IDS of 08/23/2022).
Note: SMITH is applied under both 102(a)(1) and (a)(2) date provisions; the international filing date is used as the effectively filed date, thus, no priority document is cited below.
Determining the Scope and Contents of the Prior Art:
SMITH teaches the claims 13 and 15-17 as described in ¶24, above.
STRUM teaches the instant compound lerociclib (Pg. 81 Table 1 compound GG). STRUM teaches lerociclib may be administered to a subject prior to, during, or after administration of another chemotherapeutic agent (Pg. 60 Col. 8 Lines 28-32). STRUM further teaches the subject is a human (Pg. 61 Col. 9 Lines 65-66). STRUM also teaches the compound may be administered once a day for 28 continuous days (Pg. 93 Col. 73 Lines 9 & 22-24). STRUM also teaches the use of compound lerociclib allows for the elimination of an off-cycle or drug holiday (Pg. 91 Col. 69 Lines 46-48).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
SMITH does not teach once-a-day administration for 28 continuous days.
STRUM does not teach the combination of lerociclib and erdafitinib.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treating urothelial cancer and possesses the technical knowledge necessary to make adjustments to the dosing regimen to optimize/enhance the treatment. Said artisan has also reviewed the problems in the art regarding urothelial cancer and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references SMITH (evidenced by KIM) and STRUM.
The artisan would find it obvious to administer the combination of SMITH (i.e., erdafitinib and lerociclib Form B) to the human patient with urothelial cancer once a day for 28 continuous days as taught by STRUM (Pg. 93 Col. 73 Lines 9 & 22-24). The artisan would be motivated to do so since STRUM and SMITH teach administration of the same compound (i.e., lerociclib) and since STRUM teaches lerociclib allows for the elimination of an off-cycle or drug holiday (Pg. 91 Col. 69 Lines 46-48); i.e., the dosing timeline is safe. Thus, the artisan would have a reasonable expectation that the suggested dosing timeline of STRUM would result in successful treatment of the patient of SMITH.
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.
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Claims 13 and 15-23 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1-7 and 10 of U.S. Patent No. 11,261,193 in view of:
SELVARAJ (WO 2018/039324) as evidenced by CAS RN 1702259-66-2 (American Chemical Society Chemical Abstracts Service Registry No. 1702259-66-2, available 12 May 2015, pg. 1-2),
STRUM (US 9527857, pub. 12/27/2016, cited in IDS of 08/23/2022),
ANSEL (Ansel, H.C. et al. Pharmaceutical Dosage Forms and Drug Delivery Systems, Lippincott Williams & Wilkins, 7th ed., 1999, pages 48-53), and
SMITH (WO 2019/006393, pub. 01/03/2019, effectively filed 06/29/2018, cited in IDS of 08/23/2022) as evidenced by KIM (Kim, Y.S. et al., BMC Urology, 2018, 18(68), 1-7).
Determining the Scope and Contents of the Prior Art:
Reference claims 1-7 teach the instant di-HCl crystal Form B of the instant compound
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and a pharmaceutical composition thereof.
The references SMITH (evidenced by KIM) and STRUM teach the instant claims 13 and 15-18, see ¶34 above. The references SELVARAJ (evidenced by CAS), STRUM, ANSEL, and SMITH teach the instant claims 19-23, see ¶33 above. The teachings are incorporated here by reference.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
US ‘193 does not teach the instant method of treatment in combination with an FGFR inhibitor.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treatment of hepatocellular carcinoma and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the outcomes. Said artisan has also reviewed the problems in the art regarding hepatocellular carcinoma and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims 13 and 15-18 are prima facie obvious in light of the combination of references US 11,261,193, SMITH (evidenced by KIM), and STRUM.
Regarding claims 13 and 15-18, since SMITH and US ‘193 are drawn to the same di-HCl crystal salt form of lerociclib, the artisan would recognize these references as equivalent teachings. Thus, in view of the embodiments of SMITH, the artisan would find it obvious to treat urothelial cancer via administration of lerociclib Form B and erdafitinib. The logic applied in ¶34 above, applies here for all limitations of the instant claims.
The instant claims 19-23 are prima facie obvious in light of the combination of references US 11,261,193, SELVARAJ (evidenced by CAS), STRUM, ANSEL, and SMITH.
Regarding claims 19-23, since SMITH and US ‘193 are drawn to the same di-HCl crystal salt form of lerociclib, the artisan would recognize these references as equivalent teachings. The artisan would be motivated to utilize the crystal form of the claims of US ‘193 within the method of SELVARAJ using the same logic described in ¶33, above. Since the combination of references SELVARAJ (evidenced by CAS), STRUM, ANSEL, and SMITH teach the instant claims 19-23 by the logic in ¶33, the combination thereof with US ’193 would similarly teach the instant claims.
Claims 13 and 15-23 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 9,481,691 in view of:
SELVARAJ (WO 2018/039324) as evidenced by CAS RN 1702259-66-2 (American Chemical Society Chemical Abstracts Service Registry No. 1702259-66-2, available 12 May 2015, pg. 1-2),
STRUM (US 9527857, pub. 12/27/2016, cited in IDS of 08/23/2022),
ANSEL (Ansel, H.C. et al. Pharmaceutical Dosage Forms and Drug Delivery Systems, Lippincott Williams & Wilkins, 7th ed., 1999, pages 48-53), and
SMITH (WO 2019/006393, pub. 01/03/2019, effectively filed 06/29/2018, cited in IDS of 08/23/2022) as evidenced by KIM (Kim, Y.S. et al., BMC Urology, 2018, 18(68), 1-7).
Determining the Scope and Contents of the Prior Art:
The reference claims 1-2 are drawn to the instant CDK 4/6 inhibitor (i.e., lerociclib) or salt thereof and a pharmaceutical composition thereof.
The references SMITH (evidenced by KIM) and STRUM teach the instant claims 13 and 15-18, see ¶34 above. The references SELVARAJ (evidenced by CAS), STRUM, ANSEL, and SMITH teach the instant claims 19-23, see ¶33 above. The teachings are incorporated here by reference.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
US ‘691 does not teach the instant method of treatment in combination with an FGFR inhibitor, the instant dosing regimen, nor the instant Form B.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treatment of hepatocellular carcinoma and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the outcomes. Said artisan has also reviewed the problems in the art regarding hepatocellular carcinoma and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims 13 and 15-18 are prima facie obvious in light of the combination of references US 9,481,691, SMITH (evidenced by KIM), and STRUM.
Regarding claims 13 and 15-18, since US ‘691 and SMITH are drawn to the same compound lerociclib, the artisan would recognize these references as related teachings. The artisan would be motivated to utilize the salt of lerociclib (i.e., the compound of the reference claims) as it is taught within the method of SMITH using the same logic described in ¶34, above. Since the combination of references SMITH and STRUM teach the instant claims 13 and 15-18 by the logic in ¶34, the artisan would find it obvious to use the compound of US ’691 within the prior art applications, thus, teaching the instant claims.
The instant claims 19-23 are prima facie obvious in light of the combination of references US 9,481,691, SELVARAJ (evidenced by CAS), STRUM, ANSEL, and SMITH.
Regarding claims 19-23, since US ‘691, SELVARAJ, and STRUM are drawn to the same CDK 4/6 inhibitor (i.e., lerociclib), the artisan would recognize these references as related teachings. The artisan would be motivated to utilize lerociclib (i.e., the compound of the reference claims) as it is taught within the method of SELVARAJ using the same logic described in ¶33, above. Since the combination of references SELVARAJ (evidenced by CAS), STRUM, ANSEL, and SMITH teach the instant claims 19-23 by the logic in ¶33, the artisan would find it obvious to use the compound of US ’691 within the prior art applications, thus, teaching the instant claims.
Claims 13 and 15-23 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1-3, 6, 8-9, 13-14 of U.S. Patent No. 12,364,697 in view of:
SELVARAJ (WO 2018/039324) as evidenced by CAS RN 1702259-66-2 (American Chemical Society Chemical Abstracts Service Registry No. 1702259-66-2, available 12 May 2015, pg. 1-2),
STRUM (US 9527857, pub. 12/27/2016, cited in IDS of 08/23/2022),
ANSEL (Ansel, H.C. et al. Pharmaceutical Dosage Forms and Drug Delivery Systems, Lippincott Williams & Wilkins, 7th ed., 1999, pages 48-53), and
SMITH (WO 2019/006393, pub. 01/03/2019, effectively filed 06/29/2018, cited in IDS of 08/23/2022) as evidenced by KIM (Kim, Y.S. et al., BMC Urology, 2018, 18(68), 1-7).
Determining the Scope and Contents of the Prior Art:
The reference claims 1-3 are drawn to a twice daily dosing regime for treating a human with cancer by administering the diHCl salt of the instant CDK 4/6 inhibitor (i.e., lerociclib) comprising an additional therapeutic agent. Reference claim 6 teaches the dosing regime is administered for at least 24 weeks. Reference claims 8-9 and 13-14 are drawn to wherein the cancer is liver cancer or hepatocellular carcinoma.
The references SMITH (evidenced by KIM) and STRUM teach the instant claims 13 and 15-18, see ¶34 above. The references SELVARAJ (evidenced by CAS), STRUM, ANSEL, and SMITH teach the instant claims 19-23, see ¶33 above. The teachings are incorporated here by reference.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
US ‘697 does not teach the instant method of treatment in combination with an FGFR inhibitor nor the instant Form B.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treatment of hepatocellular carcinoma and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the outcomes. Said artisan has also reviewed the problems in the art regarding hepatocellular carcinoma and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims 13 and 15-18 are prima facie obvious in light of the combination of references US 12,364,697, SMITH (evidenced by KIM), and STRUM.
Regarding claims 13 and 15-18, since US ‘697 and SMITH are drawn to the same di-HCl salt of lerociclib, the artisan would recognize these references as equivalent teachings. Thus, in view of the embodiments of SMITH, the artisan would find it obvious to treat urothelial cancer via administration of lerociclib di HCl salt and erdafitinib. The logic applied in ¶34 above, applies here for all limitations of the instant claims.
The instant claims 19-23 are prima facie obvious in light of the combination of references US 12,364,697, SELVARAJ (evidenced by CAS), STRUM, ANSEL, and SMITH.
Regarding claims 19-23, since US ‘697, SELVARAJ, and STRUM are drawn to the same CDK 4/6 inhibitor (i.e., lerociclib), and since US ‘697 and SELVARAJ both teach treatment of hepatocellular cancer (i.e., liver cancer), the artisan would recognize these references as related teachings. The artisan would be motivated to utilize lerociclib (i.e., the compound of the reference claims) as it is taught within the method of SELVARAJ using the same logic described in ¶33, above. Since the combination of references SELVARAJ (evidenced by CAS), STRUM, ANSEL, and SMITH teach the instant claims 19-23 by the logic in ¶33, the artisan would find it obvious to use the compound of US ’697 within the prior art applications, thus, teaching the instant claims.
Further, since US ‘697 teaches a dosing regime which falls within the instant dosing time frames (≥once daily and ≥28 consecutive days) for a cancer which is a species of the instant claims (hepatocellular carcinoma), the artisan would find the instant dosing regimen obvious.
Claims 13 and 15-23 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1-9, 11,13-20, 22, 24, 26-32, 34,36-40, 42, 44, and 46 of U.S. Patent No. 11,357,779 in view of:
SELVARAJ (WO 2018/039324) as evidenced by CAS RN 1702259-66-2 (American Chemical Society Chemical Abstracts Service Registry No. 1702259-66-2, available 12 May 2015, pg. 1-2),
STRUM (US 9527857, pub. 12/27/2016, cited in IDS of 08/23/2022),
ANSEL (Ansel, H.C. et al. Pharmaceutical Dosage Forms and Drug Delivery Systems, Lippincott Williams & Wilkins, 7th ed., 1999, pages 48-53), and
SMITH (WO 2019/006393, pub. 01/03/2019, effectively filed 06/29/2018, cited in IDS of 08/23/2022) as evidenced by KIM (Kim, Y.S. et al., BMC Urology, 2018, 18(68), 1-7).
Determining the Scope and Contents of the Prior Art:
The reference claims 1-6 and 14-18 are drawn to a dosing regime for treating a human with cancer by administering the diHCl crystal Form B of the instant CDK 4/6 inhibitor (i.e., instant Form B of lerociclib). Reference claims 13 and 26 teach the regime comprising an additional therapeutic agent. Reference claims 7-9, 19-20, and 22 teach the dosing regime is administered at least once or twice a day for at least 24 weeks. Reference claims 11 and 24 are drawn to wherein the cancer is liver cancer.
Reference claims 27-29 and 37-38 are drawn to a dosing regime for treating a human with cancer by administering the instant CDK 4/6 inhibitor (i.e., lerociclib). Reference claims 36 and 46 teach the regime comprising an additional therapeutic agent. Reference claims 30-32, 39-40, and 42 teach the dosing regime is administered at least once or twice a day for at least 24 weeks. Reference claims 34 and 44 are drawn to wherein the cancer is liver cancer.
The references SMITH (evidenced by KIM) and STRUM teach the instant claims 13 and 15-18, see ¶34 above. The references SELVARAJ (evidenced by CAS), STRUM, ANSEL, and SMITH teach the instant claims 19-23, see ¶33 above. The teachings are incorporated here by reference.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
US ‘779 does not teach the instant method of treatment in combination with an FGFR inhibitor.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treatment of hepatocellular carcinoma and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the outcomes. Said artisan has also reviewed the problems in the art regarding hepatocellular carcinoma and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims 13 and 15-18 are prima facie obvious in light of the combination of references US 11,357,779, SMITH (evidenced by KIM), and STRUM.
Regarding claims 13 and 15-18, since SMITH and US ‘779 are drawn to the same di-HCl crystal salt form of lerociclib, the artisan would recognize these references as equivalent teachings. Thus, in view of the embodiments of SMITH, the artisan would find it obvious to treat urothelial cancer via administration of lerociclib Form B and erdafitinib. The logic applied in ¶34 above, applies here for all limitations of the instant claims.
The instant claims 19-23 are prima facie obvious in light of the combination of references US 11,357,779, SELVARAJ (evidenced by CAS), STRUM, ANSEL, and SMITH.
Regarding claims 19-23, since US ‘779, SELVARAJ, and STRUM are drawn to the same CDK 4/6 inhibitor (i.e., lerociclib), US ‘779 and SMITH are drawn to the same diHCl crystal Form B of lerociclib, and since US ‘697 and SELVARAJ both teach treatment of liver cancer, the artisan would recognize these references as related teachings. The artisan would be motivated to utilize lerociclib and/or its Form B (i.e., the compound of the reference claims) as it is taught within the method of SELVARAJ using the same logic described in ¶33, above. Since the combination of references SELVARAJ (evidenced by CAS), STRUM, ANSEL, and SMITH teach the instant claims 19-23 by the logic in ¶33, the artisan would find it obvious to use the compound of US ’779 within the prior art applications, thus, teaching the instant claims.
Further, since US ‘779 teaches a dosing regime which falls within the instant dosing time frames (≥once daily and ≥28 consecutive days) for liver cancer which overlaps with a species of the instant claims and SELVARAJ (i.e., hepatocellular carcinoma), the artisan would find the instant dosing regimen obvious.
Conclusion
Claims 13 and 15-23 are rejected.
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/S.E.B./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625