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 instant application, filed 11/16/2023, is a 371 filing of PCT/EP2022/063629, filed 05/19/2022, and claims priority to provisional application PRO 63/253,316, filed 10/07/2021; provisional application PRO 63/242,857, filed on 09/10/2021; and PRO 63/190,602, filed on 05/19/2021.
Status of Claims
The preliminary amendment of 11/16/2023 is acknowledged. Claims 2-4, 6-21, 23, 27-28, 32-33, 45-48, and 50-61 are canceled. Claims 1, 5, 22, 24-26, 29-31, 34-44 and 49, filed on 11/16/2023, are currently pending and are examined on the merits herein.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on DATE is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Specification - Abstract
The abstract of the disclosure is objected to because the Abstract as filed on 11/16/2023 is a copy of first page of the WIPO document WO 2022/243467 A1. Applicant is reminded of the proper content of an abstract of the disclosure. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
Claim Objections
Claim 24 is objected to because of the following informalities: Claim 24 is missing a period at the end of the claim. See MPEP 608.01(m) and 37 CFR 1.75(i). Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 29, 35, 36, 37, 38, 39, 40, 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 29 which is dependent on claim 22 recites the limitation "subject" but claim 22 does not recite the limitation “subject”. There is insufficient antecedent basis for this limitation in the claim. For compact prosecution, the examiner interprets the “subject” recited in claim 29 as “the patient” in claim 22. The rejection could be overcome by amending “subject” to “patient”.
Claims 35, 37, and 39 which are dependent on claim 22 recites the limitation of “said FGFR inhibitor”. Claim 22 only recites erdafitinib. There is insufficient antecedent basis for this limitation. The rejection could be overcome by amending “said FGFR inhibitor” to “erdafitinib”.
Claim 36, 38, and 40 recite the phrase “in particular” which renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. One cannot tell if the limitation “in particular wherein the erdafitinib is administered at a dose…” is part of the claimed invention or exemplary language. See MPEP § 2173.05(d).
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.
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 1, 5, 22, 24, 25, 26, 29, 34, 35, 36, 41, and 42 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020/243273 A2, published on 12/03/2020, herein referred to as Panicucci 2020 and in further view of Tabernero et al., 2015 (Tabernero et al., "Phase I Dose-Escalation Study of JNJ-42756493, an Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients With Advanced Solid Tumors", J. Clin. Oncol., 2015, 33, 3401-3408, listed in the IDS 05/31/2024) and FDA drug label BALVERSA, 2019 (BALVERSA, FDA drug label, version April 2019, website: www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf).
Regarding instant claims 1, 5, 22, 24, and 25, Panicucci 2020 teaches a method of treating cancer, said method comprising administering a therapeutically effective amount of erdafitinib to a patient who has been diagnosed with cancer and who harbors at least one fibroblast growth factor receptor (FGFR) fusion selected from claim 1 which is FGFR2-CCDC147 and the cancer is cholangiocarcinoma (page 17, paragraph 0080, “In one aspect, provided herein are methods of treating cholangiocarcinoma in a patient in need thereof”; page 18, paragraph 0086, “the receptor tyrosine kinase inhibitor is a selective non-covalently binding inhibitor of FGFR1, FGFR2, FGFR3 and/or FGFR4 is selected from the group consisting of erdafitinib” and page 19, paragraph 0091, “In certain embodiments, the cholangiocarcinoma has a FGFR2 gene fusion, translocation or another genetic alteration. […]the FGFR2 gene fusion comprises a FGFR2 gene fusion partner selected from the group consisting of […] CCDC147”).
Regarding instant claim 26, Panicucci 2020 teaches one FGFR genetic alteration is FGFR1-BAG4 and FGFR3-TACC3 (page 19, paragraph 0090, “FGFR1 gene fusion partner selected from the group consisting of BAG4” and paragraph 0092, “FGFR3 gene fusion partner, wherein the FGFR gene fusion partner is TACC3”).
Regarding instant claim 29, Panicucci 2020 teaches that the subject received at least one line of systemic therapy prior to administration of erdafitinib (page 18, paragraph 0083, “the previous administration of another therapy is administration of another chemotherapeutic agent”).
Regarding instant claims 34, 35, and 36, Panicucci 2020 teaches a method of treating cancer said method comprising administering erdafitinib. However, Panicucci 2020 does not teach the dosing regimen of erdafitinib for patients 15 years or older or at the date of first administration of erdafitinib and wherein the patients are administered at a dose of about 8 mg once daily. Tabernero et al., 2015 teaches a dosing regimen of erdafitinib to treat advanced solid tumors for patients 18 years and older (Title and page 2, column 1, Patients, “Patients with histologically or cytologically confirmed, advanced solid tumors for which standard curative treatment is no longer effective; age ≥ 18 years”). Applicant’s specification recites that the JNJ-42756493 is erdafitinib (page 32, line 8, “N-(3,5-dimethoxyphenyl)-N'-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]ethane-1,2-diamine (referred to herein "JNJ-42756493" or "JNJ493" or erdafitinib”). Further, Tabernero et al., 2015 teaches daily dose ranges from 0.5-12mg to determine the recommended phase II dose (RP2D) of erdafitinib and discloses that erdafitinib demonstrated a challenging but manageable safety profile (page 2, column 1, study design, “escalating multiple dose cohorts (0.5, 2, 4, 6, 9, and 12 mg) with a daily dosing schedule (21-day cycles) and the cohorts of 10 or 12 mg on a 7-day son/7-days-off intermittent schedule (28-day cycles)” and page 7, column 2, “JNJ-42756493 demonstrated a challenging but manageable safety profile anticipated with inhibition of FGFR signaling and preliminary antitumor activity in a heavily pretreated patient population”).
Therefore, it would have been obvious to the person of ordinary skill in the art to use dosing regimen as taught by Tabernero et al., 2015 and expect reasonable success at inducing effective anti-tumor activity while limiting dose toxicities. Further, the dosage in a composition is clearly a result effective parameter that a person having ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been obvious for an artisan of ordinary skill to determine the optimal amount of each ingredient, i.e., the dosage and dosing regimen, needed to achieve the desired results. The principle of law states from MPEP §§ 2144.05: "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," (see In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382). 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," (See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)).
Regarding instant claims 41 and 42, Panicucci 2020 teaches that an FGFR inhibitor is a tablet which is a solid dosage form (page 11, paragraph 0050, “As used herein, "solid dosage form" means a pharmaceutical dose(s) in solid form, e.g., tablets [...]”) but does not teach the dosage form of the erdafitinib. The FDA drug label BALVERSA or also known as erdafitinib is n tablet form (page 1, column 1, “BALVERSA (erdafitinib), tablets, for oral use”). Further, the FDA drug label BALVERSA discloses the tablets are taken daily orally and with and without food (page 1, Dosage and administration, “recommended initial dosage: 8 mg orally once daily with a dose increase to 9 mg daily if criteria are met. Swallow whole with or without food”). Therefore, it would have been obvious to the person of ordinary skill in the art to include the tablet dosage form BALVERSA to allow daily oral dosage.
Claims 37, 38, 39, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Panicucci 2020 (cited previously), Tabernero et al., 2015 (cited previously), and FDA drug label BALVERSA, 2019 (cited previously) as applied to claim 22 above and in further view of Barker et al., 2018 (Barker et al. Pharmacokinetic studies in children: recommendations for practice and research. Arch Dis Child. 2018 Jul;103(7):695-702. doi: 10.1136/archdischild-2017-314506. Epub 2018 Apr 19. PMID: 29674514; PMCID: PMC6047150).
Regarding claims 37, 38, 39, and 40, while Panicucci 2020, Tabernero et al., 2020, and FDA drug label BALVERSA, 2019 do not teach the dosing regimen for patients that are between 12 years of age and <15 years of age (claim 37) 6 years of age and <12 years of age (claim 39).
Barker et al., 2018 teaches allometric scaling method to determine pediatric doses based on PK profiles of adult doses (page 698, column 1, “Allometric scaling of clearance a priori is now common in PK modelling and is an appropriate way to scale fore size in children over 2 years of age”). As Tabernero et al., 2015 teaches adult dosages and ranges with a safe tolerability profile of erdafitinib (page 5, column 1, “JNJ-42756493 has a high (in vitro) permeability and solubility, and its plasma PK is linear and time independent across the tested dose range of 0.5 to 12 mg” and page 7, column 2, “The 10-mg 7-days-on/7-days-off dose regimen has been selected as the optimal RP2D because it had the best safety and tolerability profile and also achieved clinical exposures in the efficacious range”), it would have been obvious to the person of ordinary skill in the art to use allometric scaling taught by Barker et al., 2018 to determine pediatric doses based on safe and tolerable adult doses taught by Tabernero and expect reasonable success at limiting toxicities to the drug for patients under 12 years of age. Further, the dosage in a composition is clearly a result effective parameter that a person having ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been obvious for an artisan of ordinary skill to determine the optimal amount of each ingredient, i.e., the dosage and dosing regimen, needed to achieve the desired results. The principle of law states from MPEP §§ 2144.05: "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," (see In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382). 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," (See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)).
Claims 30, 31, 43, 44, and 49 are rejected under 35 U.S.C. 103 as being unpatentable over Panicucci 2020 (cited previously), Tabernero et al., 2015 (cited previously), FDA drug label for BALVERSA, 2019 (cited previously) as applied to claim 22 above and in further view of US 2015/023589 A1, published on 07/23/2015, herein referred to as Iavarone 2015.
Regarding instant claim 30, 31, 43 and 49 while Panicucci 2020, Tabernero et al., 2015 and the FDA drug label for BALVERSA, 2019 teach a method of treating cancer comprising administering a therapeutically effective amount of erdafitinib as described above, they do not teach evaluating a biological sample from the patient for the presence of the at least one FGFR fusion or the at least one FGFR genetic alteration prior to said administration of erdafitinib and wherein the biological sample is blood, lymph fluid, bone marrow, a solid tumor sample, or any combination thereof. Iavarone 2015 teaches a method of treating cancer comprising obtaining a sample from the subject in need thereof to determine the level of expression of an FGFR fusion molecule in the subject prior to administering erdafitinib (page 69, paragraph 0257, column 1, “The present invention provides a method for treating a gene-fusion associated cancer in a subject in need thereof. In one embodiment, the method comprises obtaining a sample from the subject to determine the level of expression of an FGFR fusion molecule in the subject” and “In some embodiments, the method further comprises assessing whether to administer a FGFR fusion molecule inhibitor based on the expression pattern of the subject. In further embodiments, the method comprises administering a FGFR fusion molecule inhibitor to the subject. In one embodiment, the FGFR fusion molecule inhibitor is JNJ-42756493”). Iavarone 2015 further describes that the biological sample is a tumor sample (page 4, paragraph 0045, “An aspect of the invention provides for a method for detecting the presence of a FGFR fusion in a human subject. In one embodiment, the method comprises obtaining a biological sample from the human subject. In some embodiments the sample from the subject is a tissue sample. […] the tissue sample from the subject is a tumor sample”). Iavarone 2015 also discloses the FGFR fusion molecule present in a biological sample is FGFR2-CCDC147 recited in claim 43 (page 58, paragraph 0196, “A FGFR fusion molecule can also include a tyrosine kinase domain of an FGFR protein fused to a protein encoded by any one of the genes listed in Table 7. See in Table 7. Fusion Partners: CCDC147”). Iavarone 2015 discloses that “the strong antitumor effects obtained with JNJ-42756493 in glioma cells harboring FGFR3-TACC3 fusions have built a compelling rationale for the treatment of glioma patients positive for FGFR-TACC rearrangements” (page 116, paragraph 0496). Therefore, it would have been obvious to the person of ordinary skill in the art to use the method of detecting FGFR fusion or genetic alteration in a sample of a cancer patient before administering erdafitinib to the patient as taught by Iavarone 2015 and expect reasonable success at inducing strong antitumor effects.
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.
Nonstatutory Double Patenting to U.S. Patents
Claims 1, 5, 22, 24-26, 29-31, 34-43, and 49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 5, 9, 12, 13, 14, 15, 17, 19, 21, and 23 of U.S. Patent No. 11077106 B2 herein referred to as Pat106 in view of Panicucci 2020 (cited previously), Tabernero et al., 2015 (cited previously), Iavarone 2015 (cited previously), Barker et al., 2018 (cited previously) and Bahleda et al., 2019 (Bahleda et al. Multicenter Phase I Study of Erdafitinib (JNJ-42756493), Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients with Advanced or Refractory Solid Tumors. Clin Cancer Res. 2019 Aug 15;25(16):4888-4897. doi: 10.1158/1078-0432.CCR-18-3334. Epub 2019 May 14).
Regarding instant claims 1, 5, 22, 25, 36, 43, and 49, Pat 106 claim 1 recites a method for the treatment of urothelial cancer harboring at least one FGFR genomic alteration, which method comprises administering to a subject in need thereof, 8 mg of erdafitinib daily on a continuous basis.
Regarding instant claim 26, Pat106 claims 12, 13, 14, 15, 17, and 19 recite the FGFR genomic alteration is an FGFR3-TACC3 translocation (Pat106 claim 12 and 17), FGFR3 R248C, FGFR3 S249C (Pat106 claim 13 and 18), FGFR2:BICC1 ( Pat106 claim 14 and 19), FGFR3-TACC3 fusion (Pat106 claim 15).
Regarding instant claims 36, Pat106 claim 2, 5, and 9 recite the erdafitinib daily dose is 8 mg, 9 mg and 6 mg.
However, Pat106 does not recite optimizing dosing regimen based on patients age as recited in instant claims 35, 37, 38, 39, and 40. Tabernero et al., 2015 teaches daily dose ranges from 0.5-12mg to determine the recommended phase II dose (RP2D) of erdafitinib and discloses that erdafitinib demonstrated a challenging but manageable safety profile (page 2, column 1, study design, “escalating multiple dose cohorts (0.5, 2, 4, 6, 9, and 12 mg) with a daily dosing schedule (21-day cycles) and the cohorts of 10 or 12 mg” and page 7, column 2, “JNJ-42756493 demonstrated a challenging but manageable safety profile anticipated with inhibition of FGFR signaling and preliminary antitumor activity in a heavily pretreated patient population”). Further, Barker et al., 2018 teaches allometric scaling method to determine pediatric doses based on PK profiles of adult doses (page 698, column 1, “Allometric scaling of clearance a priori is now common in PK modelling and is an appropriate way to scale fore size in children over 2 years of age”). As Tabernero et al., 2015 teaches adult dosages and ranges with a safe tolerability profile of erdafitinib (page 5, column 1, “JNJ-42756493 has a high (in vitro) permeability and solubility, and its plasma PK is linear and time independent across the tested dose range of 0.5 to 12 mg” and page 7, column 2, “The 10-mg 7-days-on/7-days-off dose regimen has been selected as the optimal RP2D because it had the best safety and tolerability profile and also achieved clinical exposures in the efficacious range”), it would have been obvious to the person of ordinary skill in the art to use allometric scaling taught by Barker et al., 2018 to determine pediatric doses based on safe and tolerable adult doses taught by Tabernero and expect reasonable success at limiting toxicities to the drug for patients under 12 years of age. Further, the dosage in a composition is clearly a result effective parameter that a person having ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been obvious for an artisan of ordinary skill to determine the optimal amount of each ingredient, i.e., the dosage and dosing regimen, needed to achieve the desired results. The principle of law states from MPEP §§ 2144.05: "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," (see In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382). 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," (See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)).
Pat106 claims do not recite evaluating a biological sample from the patient for the presence of the at least one FGFR genetic alteration prior to administration of erdafitinib as recited in instant claim 30 and wherein the biological sample is blood, lymph fluid, bone marrow, a solid tumor sample as recited in instant claim 31. Iavarone 2015 teaches a method of treating cancer comprising obtaining a sample from the subject in need thereof to determine the level of expression of an FGFR fusion molecule in the subject prior to administering erdafitinib (page 69, paragraph 0257, column 1, “The present invention provides a method for treating a gene-fusion associated cancer in a subject in need thereof. In one embodiment, the method comprises obtaining a sample from the subject to determine the level of expression of an FGFR fusion molecule in the subject” and “In some embodiments, the method further comprises assessing whether to administer a FGFR fusion molecule inhibitor based on the expression pattern of the subject. In further embodiments, the method comprises administering a FGFR fusion molecule inhibitor to the subject. In one embodiment, the FGFR fusion molecule inhibitor is JNJ-42756493”). Iavarone 2015 further describes that the biological sample is a tumor sample (page 4, paragraph 0045, “An aspect of the invention provides for a method for detecting the presence of a FGFR fusion in a human subject. In one embodiment, the method comprises obtaining a biological sample from the human subject. In some embodiments the sample from the subject is a tissue sample. […] the tissue sample from the subject is a tumor sample”). Iavarone 2015 discloses that “the strong antitumor effects obtained with JNJ-42756493 in glioma cells harboring FGFR3-TACC3 fusions have built a compelling rationale for the treatment of glioma patients positive for FGFR-TACC rearrangements” (page 116, paragraph 0496). Therefore, it would have been obvious to the person of ordinary skill in the art to use the method of detecting FGFR fusion or genetic alteration in a sample of a cancer patient before administering erdafitinib to the patient as taught by Iavarone 2015 and expect reasonable success at inducing strong antitumor effects.
Regarding instant claims 41 and 42, Pat106 claims 21 and 23 recite erdafitinib in tablet form. Pat106 claims do not recite cancers as recited in instant claims 5, 22, and 24 and Pat106 claims do not recite FGFR genomic alterations recited in claim 1, 5, and 43. Panicucci 2020 teaches a method of treating cancer, said method comprising administering a therapeutically effective amount of erdafitinib to a patient who has been diagnosed with cancer and who harbors at least one fibroblast growth factor receptor (FGFR) fusion selected from claim 1 which is FGFR2-CCDC147 and the cancer is cholangiocarcinoma (page 17, paragraph 0080, “In one aspect, provided herein are methods of treating cholangiocarcinoma in a patient in need thereof”; page 18, paragraph 0086, “the receptor tyrosine kinase inhibitor is a selective non-covalently binding inhibitor of FGFR1, FGFR2, FGFR3 and/or FGFR4 is selected from the group consisting of erdafitinib” and page 19, paragraph 0091, “In certain embodiments, the cholangiocarcinoma has a FGFR2 gene fusion, translocation or another genetic alteration. […]the FGFR2 gene fusion comprises a FGFR2 gene fusion partner selected from the group consisting of […] CCDC147”). Further, Bahleda et al., 2019 teaches that the erdafitinib is tolerable and preliminary clinical activity in advanced solid tumors with genomic changes in the FGFR pathway with encouraging responses in urothelial carcinoma and cholangiocarcinoma (page 4888, abstract, conclusions). It would have been obvious to the person of ordinary skill in the art to use erdafitinib to treat other cancers that harbor FGFR gene alterations and expect clinical activity against cholangiocarcinoma.
Pat106 claims do not recite the subject received at least one line of systemic therapy prior to said administration of erdafitinib as recited in instant claim 29. Panicucci 2020 teaches that the subject received at least one line of systemic therapy prior to administration of erdafitinib (page 18, paragraph 0083, “the previous administration of another therapy is administration of another chemotherapeutic agent”). Panicucci 2020 teaches that cholangiocarcinoma patients relapse after first line of therapy and have few therapeutic options (page 3, line 29-31). It would have been obvious to the person of ordinary skill in the art to use erdafitinib in patients with cholangiocarcinoma that relapsed after first line therapy and have few options for second line standard of care.
Claims 1, 5, 22, 24-26, 29-31, 34-43, and 49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 2, 12, 13, and 15 of U.S. Patent No. 12350266 B2, herein referred to as Pat266 in view of Panicucci 2020 (cited previously), Tabernero et al., 2015 (cited previously), Iavarone 2015 (cited previously), Barker et al., 2018 (cited previously), FDA Drug Label for BALVERSA, 2019 (cited previously) and Bahleda et al., 2019 (cited previously).
Regarding instant claim 1, 5, 22, 25, 30, 43, and 49, Pat266 claim 1 recites a method of treating cholangiocarcinoma in a patient comprising: evaluating a biological sample from the patient for the presence of one or more FGFR mutants; and treating the patient with erdafitinib if one or more FGFR mutants are present in the sample.
Pat266 claims do not teach the biological sample is blood, lymph fluid, bone marrow, a solid tumor sample, or any combination thereof as recited in instant claim 31. As described above, Iavarone 2015 teaches a method of treating cancer comprising obtaining a sample from the subject in need thereof to determine the level of expression of an FGFR fusion molecule in the subject prior to administering erdafitinib (page 69, paragraph 0257, column 1). Iavarone 2015 further describes that the biological sample is a tumor sample (page 4, paragraph 0045). Iavarone 2015 discloses that “the strong antitumor effects obtained with JNJ-42756493 in glioma cells harboring FGFR3-TACC3 fusions have built a compelling rationale for the treatment of glioma patients positive for FGFR-TACC rearrangements” (page 116, paragraph 0496). Therefore, it would have been obvious to the person of ordinary skill in the art to use the method of detecting FGFR fusion or genetic alteration in a biological sample of a cancer patient before administering erdafitinib as taught by Iavarone 2015 and expect reasonable success at inducing strong antitumor effects.
Regarding instant claim 26, Pat266 claim 12, 13, and 15 recite the one or more FGFR mutants are selected from FGFR-BICC1 and FGFR2-KIAA1598.
Pat266 does not teach FGFR fusions as recited in claim 1, 5, and 43. As described above, Panicucci 2020 teaches a method of treating cancer, said method comprising administering a therapeutically effective amount of erdafitinib to a patient who has been diagnosed with cancer and who harbors at least one fibroblast growth factor receptor (FGFR) fusion selected from claim 1 which is FGFR2-CCDC147 and the cancer is cholangiocarcinoma (page 17, paragraph 0080; page 18, paragraph 0086, and page 19, paragraph 0091). Further, Bahleda et al., 2019 teaches that the erdafitinib is tolerable and preliminary clinical activity in advanced solid tumors with genomic changes in the FGFR pathway with encouraging responses in urothelial carcinoma and cholangiocarcinoma (page 4888, abstract, conclusions). It would have been obvious to the person of ordinary skill in the art to use erdafitinib to treat other cancers that harbor FGFR gene alterations and expect clinical activity against cholangiocarcinoma.
Pat266 does not teach the subject received at least one line of systemic therapy prior to said administration of erdafitinib as recited in instant claim 29. As described previously, Panicucci 2020 teaches that the subject received at least one line of systemic therapy prior to administration of erdafitinib (page 18, paragraph 0083). Panicucci 2020 teaches that cholangiocarcinoma patients relapse after first line of therapy and have few therapeutic options (page 3, line 29-31). It would have been obvious to the person of ordinary skill in the art to use erdafitinib in patients with cholangiocarcinoma that relapsed after first line therapy and have few options for second line standard of care.
Regarding instant claim 36, Pat266 claim 2 and 20 recite erdafitinib is administered at a dose of 8 mg once daily.
While Pat266 teaches 8 mg erdafitinib doses, Pat266 does not teach erdafitinib dosing for patients based on age as recited in instant claims 35, 37, 38, 39, and 40. As described previously, Tabernero et al., 2015 teaches daily dose ranges from 0.5-12mg to determine the recommended phase II dose (RP2D) of erdafitinib and discloses that erdafitinib demonstrated a challenging but manageable safety profile (page 2, column 1, study design). Further, Barker et al., 2018 teaches allometric scaling method to determine pediatric doses based on PK profiles of adult doses (page 698, column 1). As Tabernero et al., 2015 teaches adult dosages and ranges with a safe tolerability profile of erdafitinib (page 5, column 1), it would have been obvious to the person of ordinary skill in the art to use allometric scaling taught by Barker et al., 2018 to determine pediatric doses based on safe and tolerable adult doses taught by Tabernero and expect reasonable success at limiting toxicities to the drug for patients under 12 years of age. Further, the dosage in a composition is clearly a result effective parameter that a person having ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been obvious for an artisan of ordinary skill to determine the optimal amount of each ingredient, i.e., the dosage and dosing regimen, needed to achieve the desired results. See MPEP §§ 2144.05; In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382; and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Pat266 claims do not recite the erdafitinib is a tablet which is a solid dosage form as recited in instant claims 41 and 42. Panicucci 2020 teaches that an FGFR inhibitor is a tablet which is solid dosage form (page 11, paragraph 0050, “As used herein, "solid dosage form" means a pharmaceutical dose(s) in solid form, e.g., tablets [...]”) but does not teach the dosage form of the erdafitinib. The FDA drug label BALVERSA or also known as erdafitinib is n tablet form (page 1, column 1, “BALVERSA (erdafitinib), tablets, for oral use”). Further, the FDA drug label BALVERSA discloses the tablets are taken daily orally and with and without food (page 1, Dosage and administration, “recommended initial dosage: 8 mg orally once daily with a dose increase to 9 mg daily if criteria are met. Swallow whole with or without food”). Therefore, it would have been obvious to the person of ordinary skill in the art to include the tablet dosage form BALVERSA to allow daily oral dosage.
Claims 1, 5, 22, 24-26, 29-31, 34-43, and 49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 6, 10, 12, 13, 17, 18, 19, 20, 21, and 22 of U.S. Patent No. 12133851 B2, herein referred to as Pat851 in view of Panicucci 2020 (cited previously), FDA drug label for BALVERSA, 2019 (cited previously), Tabernero et al., 2015 (cited previously), Iavarone 2015 (cited previously), Barker et al., 2018 (cited previously) and Bahleda et al., 2019 (cited previously).
Regarding instant claim 1, 5, 22, 25, 26, 30, 43, and 49, Pat851 claim 1 and 2 recite a method of treating cholangiocarcinoma in a patient comprising determining that a biological sample from the patient comprises one or more FGFR mutants including at least the fusion FGFR2-TACC2, and administering erdafitinib or a pharmaceutically acceptable salt thereof to said patient.
Pat851 claims do not recite recites that the erdafitinib is a tablet which is a solid dosage form as recited in instant claims 41 and 42. As described previously, Panicucci 2020 teaches that an FGFR inhibitor is a tablet which is solid dosage form (page 11, paragraph 0050) but does not teach the dosage form of the erdafitinib. The FDA drug label BALVERSA or also known as erdafitinib is n tablet form (page 1, column 1). Further, the FDA drug label BALVERSA discloses the tablets are taken daily orally and with and without food (page 1, Dosage and administration). Therefore, it would have been obvious to the person of ordinary skill in the art to include the tablet dosage form BALVERSA to allow daily oral dosage.
Regarding instant claims 34 and 36, Pat851 claim 4 and 10 recite the erdafitinib is administered at a dose of 8 mg once daily.
However, Pat851 does not recite optimizing dosing of the erdafitinib based on age as recited in instant claims 35, 37, 38, 39, and 40. As described previously, Tabernero et al., 2015 teaches daily dose ranges from 0.5-12mg to determine the recommended phase II dose (RP2D) of erdafitinib and discloses that erdafitinib demonstrated a challenging but manageable safety profile (page 2, column 1, study design). Further, Barker et al., 2018 teaches allometric scaling method to determine pediatric doses based on PK profiles of adult doses (page 698, column 1). As Tabernero et al., 2015 teaches adult dosages and ranges with a safe tolerability profile of erdafitinib (page 5, column 1), it would have been obvious to the person of ordinary skill in the art to use allometric scaling taught by Barker et al., 2018 to determine pediatric doses based on safe and tolerable adult doses taught by Tabernero and expect reasonable success at limiting toxicities to the drug for patients under 12 years of age. Further, the dosage in a composition is clearly a result effective parameter that a person having ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been obvious for an artisan of ordinary skill to determine the optimal amount of each ingredient, i.e., the dosage and dosing regimen, needed to achieve the desired results. See MPEP §§ 2144.05; In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382; and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding instant claims 30, 31, and 43, Pat851 claims 6, 13, 21, and 22 recite the method of evaluating the biological sample from the patient for the presence of FGFR mutation, wherein the biological sample is blood, lymph fluid, bone marrow, solid tumor, or any combination thereof.
Regarding instant claim 26, Pat851 claims 12, 17, 18, 19, and 20 recites the method comprises determining that the biological sample from the patient comprises the fusion FGFR2-TACC2.
While Pat851 claims 1 and 2 recite cholangiocarcinoma as the cancer that erdafitinib can be applied to as recited in instant claims 22, 23, 24, and 43, Pat851 claims do not recite that the FGFR fusion is FGFR2-CCDC147, FGFR2-ENOX1, FGFR2-LCN10, FGFR2-PDE3A, FGFR2-RANBP2, or RRM2B-FGFR2 and the cancer is cholangiocarcinoma in instant claim 1, 5, and 43. As described above, Panicucci 2020 teaches a method of treating cancer, said method comprising administering a therapeutically effective amount of erdafitinib to a patient who has been diagnosed with cancer and who harbors at least one fibroblast growth factor receptor (FGFR) fusion selected from claim 1 which is FGFR2-CCDC147 and the cancer is cholangiocarcinoma (page 17, paragraph 0080; page 18, paragraph 0086, and page 19, paragraph 0091). Further, Bahleda et al., 2019 teaches that the erdafitinib is tolerable and preliminary clinical activity in advanced solid tumors with genomic changes in the FGFR pathway with encouraging responses in urothelial carcinoma and cholangiocarcinoma (page 4888, abstract, conclusions). It would have been obvious to the person of ordinary skill in the art to use erdafitinib to treat other cancers that harbor FGFR gene alterations and expect clinical activity against cholangiocarcinoma.
Pat851 claims do not recite the subject received at least one line of systemic therapy prior to said administration of erdafitinib. As described previously, Panicucci 2020 teaches that the subject received at least one line of systemic therapy prior to administration of erdafitinib (page 18, paragraph 0083). Panicucci 2020 teaches that cholangiocarcinoma patients relapse after first line of therapy and have few therapeutic options (page 3, line 29-31). It would have been obvious to the person of ordinary skill in the art to use erdafitinib in patients with cholangiocarcinoma that relapsed after first line therapy and have few options for second line standard of care.
Provisional Nonstatutory Double Patenting to Co-pending U.S. Patent Applications
Claims 1, 5, 22, 24-26, 29-31, 34-43, and 49 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 19, 46, 47, 48, 49, 60, 61, 62, and 63 of copending Application No. 17/430,025, herein referred to as App025 in view of Panicucci 2020 (cited previously), Tabernero et al., 2015 (cited previously), Iavarone 2015 (cited previously), Barker et al., 2018 (cited previously) and Bahleda et al., 2019 (cited previously). At of the time of the office action, App025 was issued a notice of allowance on 03/19/2026, since official patent issuance is pending, the nonstatutory double patenting rejection is provisional.
Regarding instant claims 1, 5, 22, 25, 35, 36, 43, and 49, App025 claim 19 and 47 recites a method for the treatment of metastatic or surgically unresectable urothelial cancer said method comprising administering to a patient in need thereof 8 mg of erdafitinib once daily, on a continuous basis, wherein patient is aged > 75 and has visceral metastasis. App025 claim 46 recites a method comprising administering to the patient 8 mg of erdafitinib once daily on a continuous basis. App025 claim 47 recite the cancer is metastatic or surgically unresectable urothelial cancer harboring select FGFR genetic alterations.
Regarding instant claims 36, 41, and 42, App025 claims 48, 49, and 63 recite a method of administering erdafitinib tablet to a patient with varying amounts to total 8 mg dose of erdafitinib.
Regarding instant claim 26, App025 claim 60, 61 and 62 recite the cancer harbors an alteration selected from the following fusions FGFR3:TACC3 v1; FGFR3:TACC3 v3; FGFR3:TACC3 Intron; FGFR3:BAIA P2L1; FGFR2:AFF3; FGFR2:BICC1; FGFR2:CASP7; FGFR2:CCDC6 and FGFR2:OFD1 and wherein the cancer is metastatic or surgically unresectable urothelial cancer with a FGFR3-TACC3 translocations (claim 61), and wherein the cancer is metastatic or surgically unresectable urothelial cancer harboring at least one of the following FGFR3 gene mutations: FGFR3 R248C, FGFR3 S249C (claim 62).
App025 do not recite FGFR gene alterations as recited in instant claims 1, 5, 43, and 44 and App025 do not teach the cancers recited in instant claims 5, 22, and 24. As described above, Panicucci 2020 teaches a method of treating cancer, said method comprising administering a therapeutically effective amount of erdafitinib to a patient who has been diagnosed with cancer and who harbors at least one fibroblast growth factor receptor (FGFR) fusion selected from claim 1 which is FGFR2-CCDC147 and the cancer is cholangiocarcinoma (page 17, paragraph 0080; page 18, paragraph 0086; and page 19, paragraph 0091). Further, Bahleda et al., 2019 teaches that the erdafitinib is tolerable and preliminary clinical activity in advanced solid tumors with genomic changes in the FGFR pathway with encouraging responses in urothelial carcinoma and cholangiocarcinoma (page 4888, abstract, conclusions). It would have been obvious to the person of ordinary skill in the art to use erdafitinib to treat other cancers that harbor FGFR gene alterations and expect clinical activity against cancer.
App025 claims do not recite the subject received at least one line of systemic therapy prior to said administration of erdafitinib. As described above, Panicucci 2020 teaches that the subject received at least one line of systemic therapy prior to administration of erdafitinib (page 18, paragraph 0083). Panicucci 2020 teaches that cholangiocarcinoma patients relapse after first line of therapy and have few therapeutic options (page 3, line 29-31). It would have been obvious to the person of ordinary skill in the art to use erdafitinib in patients with cholangiocarcinoma that relapsed after first line therapy and have few options for second line standard of care.
App025 claims do not recite evaluating the biological sample for the presence of FGFR gene alteration as recited in claims 30, 31, and 43. As described previously, Iavarone 2015 teaches a method of treating cancer comprising obtaining a sample from the subject in need thereof to determine the level of expression of an FGFR fusion molecule in the subject prior to administering erdafitinib (page 69, paragraph 0257, column 1). Iavarone 2015 further describes that the biological sample is a tumor sample (page 4, paragraph 0045). Iavarone 2015 discloses that “the strong antitumor effects obtained with JNJ-42756493 in glioma cells harboring FGFR3-TACC3 fusions have built a compelling rationale for the treatment of glioma patients positive for FGFR-TACC rearrangements” (page 116, paragraph 0496). Therefore, it would have been obvious to the person of ordinary skill in the art to use the method of detecting FGFR fusion or genetic alteration in a sample of a cancer patient before administering erdafitinib to the patient as taught by Iavarone 2015 and expect reasonable success at inducing strong antitumor effects.
App025 does not recite optimizing dosing of the erdafitinib based on age as recited in instant claims 35, 37, 38, 39, and 40. As described previously, Tabernero et al., 2015 teaches daily dose ranges from 0.5-12mg to determine the recommended phase II dose (RP2D) of erdafitinib and discloses that erdafitinib demonstrated a challenging but manageable safety profile (page 2, column 1, study design). Further, Barker et al., 2018 teaches allometric scaling method to determine pediatric doses based on PK profiles of adult doses (page 698, column 1). As Tabernero et al., 2015 teaches adult dosages and ranges with a safe tolerability profile of erdafitinib (page 5, column 1), it would have been obvious to the person of ordinary skill in the art to use allometric scaling taught by Barker et al., 2018 to determine pediatric doses based on safe and tolerable adult doses taught by Tabernero and expect reasonable success at limiting toxicities to the drug for patients under 12 years of age. Further, the dosage in a composition is clearly a result effective parameter that a person having ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been obvious for an artisan of ordinary skill to determine the optimal amount of each ingredient, i.e., the dosage and dosing regimen, needed to achieve the desired results. See MPEP §§ 2144.05; In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382; and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
This is a provisional nonstatutory double patenting rejection.
Claims 1, 5, 22, 24-26, 29-31, 34-43, and 49 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 69, 50, 51, 53, 54, 55, 60, 61, 62, 63, 70, 65, and 66 of copending Application No. 17/598,985, herein referred to as App985 in view of Panicucci 2020 (cited previously), Tabernero et al., 2015 (cited previously), Iavarone 2015 (cited previously), Barker et al., 2018 (cited previously) and Bahleda et al., 2019 (cited previously).
Regarding instant claims 1, 5, 25, 43, and 49, App985 claim 1 and 69 recites a method of treating urothelial carcinoma, the method comprising administering erdafitinib base or a pharmaceutically acceptable salt thereof to a patient and that the cancer harbors a FGFR3 genetic alteration.
Regarding instant claim 26, App985 claims 50 and 51 recite that the FGFR2 or FGFR3 alteration (claim 50) is a FGFR3 gene mutation R248C, S249C, G370C, or Y373C, or any combination thereof (claim 51) or a FGFR2 or FGFR3 gene fusion is FGFR3- TACC3, FGFR3-BAIA P2L1, FGFR2-BICC1, or FGFR2-CASP7, or any combination thereof.
Regarding instant claim 30, 31, and 43, App985 claim 53 and 54 recite the method for evaluating a biological sample from the patient for the presence of one or more FGFR2 or FGFR3 genetic alterations prior to administration of erdafitinib base or the pharmaceutically acceptable salt thereof and that the biological sample is blood, lymph fluid, bone marrow, a solid tumor sample, or any combination thereof.
Regarding instant claim 29, App985 claim 55 recites the patient received at least one prior therapy for the treatment of urothelial carcinoma.
Regarding instant claim 34, App985 claim 60, 61, and 62 recite the erdafitinib base or the pharmaceutically acceptable salt thereof is administered daily and orally, and on a continuous daily dosing schedule.
Regarding instant claim 36, App985 claim 63 and 70 recite the erdafitinib base or the pharmaceutically acceptable salt thereof is administered orally at a dose of about 8 mg erdafitinib base or 8 mg base equivalent of the pharmaceutically acceptable salt once daily.
Regarding instant claim 41 and 42, App 985 claims 65 and 66 recite erdafitinib base or the pharmaceutically acceptable salt thereof is present in a solid dosage form and wherein the solid dosage form is a tablet.
App985 claims do not recite optimizing dosages based on the patient’s age as recited in instant claims 35, 37, 38, 39, and 40. As described previously, Tabernero et al., 2015 teaches daily dose ranges from 0.5-12mg to determine the recommended phase II dose (RP2D) of erdafitinib and discloses that erdafitinib demonstrated a challenging but manageable safety profile (page 2, column 1, study design). Further, Barker et al., 2018 teaches allometric scaling method to determine pediatric doses based on PK profiles of adult doses (page 698, column 1). As Tabernero et al., 2015 teaches adult dosages and ranges with a safe tolerability profile of erdafitinib (page 5, column 1), it would have been obvious to the person of ordinary skill in the art to use allometric scaling taught by Barker et al., 2018 to determine pediatric doses based on safe and tolerable adult doses taught by Tabernero and expect reasonable success at limiting toxicities to the drug for patients under 12 years of age. Further, the dosage in a composition is clearly a result effective parameter that a person having ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been obvious for an artisan of ordinary skill to determine the optimal amount of each ingredient, i.e., the dosage and dosing regimen, needed to achieve the desired results. See MPEP §§ 2144.05; In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382; and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
App985 claims do not recite the cancers recited in instant claims 5, 22, and 24 and App985 do not recite the FGFR fusions or gene alterations in instant claims 1, 5, and 43.
As described above, Panicucci 2020 teaches a method of treating cancer, said method comprising administering a therapeutically effective amount of erdafitinib to a patient who has been diagnosed with cancer and who harbors at least one fibroblast growth factor receptor (FGFR) fusion selected from claim 1 which is FGFR2-CCDC147 and the cancer is cholangiocarcinoma (page 17, paragraph 0080; page 18, paragraph 0086, and page 19, paragraph 0091). Further, Bahleda et al., 2019 teaches that the erdafitinib is tolerable and preliminary clinical activity in advanced solid tumors with genomic changes in the FGFR pathway with encouraging responses in urothelial carcinoma and cholangiocarcinoma (page 4888, abstract, conclusions). It would have been obvious to the person of ordinary skill in the art to use erdafitinib to treat other cancers that harbor FGFR gene alterations and expect clinical activity against cancer.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 5, 22, 24-26, 29-31, 34-43, and 49 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 3, 15, 16, 17, 18, 20, 23, 32, and 43, of copending Application No. 17/599,729 herein referred to as App729 in view of Panicucci 2020 (cited previously), Tabernero et al., 2015 (cited previously), Iavarone 2015 (cited previously), Barker et al., 2018 (cited previously) and Bahleda et al., 2019 (cited previously). As of 03/25/2026, Application 17/599,729 has an issued allowance but there no publication at the time of this office action. Therefore, this NSDP rejection is therefore provisional.
Regarding instant claims 1, 22, 25, 26, and 43, App729 claim 2 recites a method of treating urothelial carcinoma in a patient harboring at least two FGFR3 mutations comprising FGFR3 G370C and FGFR3 S249C; FGFR3 R248C and FGFR3 Y373C; or FGFR3 S249C and FGFR3 Y373C, in a patient, the method comprising administering a FGFR inhibitor to the patient.
Regarding instant claim 30, 31, and 43, App729 claims 3 and 15 recite evaluating a biological sample from the patient for the presence of the at least two FGFR3 mutations prior to administering the FGFR inhibitor and wherein the biological sample is blood, lymph fluid, bone marrow, a solid tumor sample, or any combination thereof.
Regarding instant claims 1, 22, 43, and 49, App729 claim 16 and 32 recite the FGFR inhibitor is erdafitinib.
Regarding instant claims 34, App729 claims 17 and 18 recite the erdafitinib is administered daily and orally.
Regarding instant claim 36, App729 claim 20 and 43 recite the erdafitinib is administered orally at a dose of about 8 mg once daily.
Regarding instant claims 41 and 42, App729 claim 23 recite the erdafitinib is administered in the form of a tablet.
App729 does not recite the subject received at least one line of systemic therapy prior to said administration of erdafitinib as recited in instant claim 29. As described previously, Panicucci 2020 teaches that the subject received at least one line of systemic therapy prior to administration of erdafitinib (page 18, paragraph 0083). Panicucci 2020 teaches that cholangiocarcinoma patients relapse after first line of therapy and have few therapeutic options (page 3, line 29-31). It would have been obvious to the person of ordinary skill in the art to use erdafitinib in patients with cholangiocarcinoma that relapsed after first line therapy and have few options for second line standard of care.
App729 does not recite optimizing dosages based on the patient’s age as recited in instant claims 35, 37, 38, 39, and 40. As described previously, Tabernero et al., 2015 teaches daily dose ranges from 0.5-12mg to determine the recommended phase II dose (RP2D) of erdafitinib and discloses that erdafitinib demonstrated a challenging but manageable safety profile (page 2, column 1, study design). Further, Barker et al., 2018 teaches allometric scaling method to determine pediatric doses based on PK profiles of adult doses (page 698, column 1). As Tabernero et al., 2015 teaches adult dosages and ranges with a safe tolerability profile of erdafitinib (page 5, column 1), it would have been obvious to the person of ordinary skill in the art to use allometric scaling taught by Barker et al., 2018 to determine pediatric doses based on safe and tolerable adult doses taught by Tabernero and expect reasonable success at limiting toxicities to the drug for patients under 12 years of age. Further, the dosage in a composition is clearly a result effective parameter that a person having ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been obvious for an artisan of ordinary skill to determine the optimal amount of each ingredient, i.e., the dosage and dosing regimen, needed to achieve the desired results. See MPEP §§ 2144.05; In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382; and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
App729 does not recite the cancers recited in instant claims 5, 22, and 24 and App729 does not recite the FGFR gene alteration as recited in instant claims 1, 5, 43, and 44. As described above, Panicucci 2020 teaches a method of treating cancer, said method comprising administering a therapeutically effective amount of erdafitinib to a patient who has been diagnosed with cancer and who harbors at least one fibroblast growth factor receptor (FGFR) fusion selected from claim 1 which is FGFR2-CCDC147 and the cancer is cholangiocarcinoma (page 17, paragraph 0080; page 18, paragraph 0086; and page 19, paragraph 0091). Further, Bahleda et al., 2019 teaches that the erdafitinib is tolerable and preliminary clinical activity in advanced solid tumors with genomic changes in the FGFR pathway with encouraging responses in urothelial carcinoma and cholangiocarcinoma (page 4888, abstract, conclusions). It would have been obvious to the person of ordinary skill in the art to use erdafitinib to treat other cancers that harbor FGFR gene alterations and expect clinical activity against cancer.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 5, 22, 24-26, 29-31, 34-43, and 49 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 23, 24, 30, 31, 32, 33, 25, 26, 51, 52, 54, 55, 56, 58, 59, and 60 of copending Application No. 17/904,139 herein referred to as App139 in view of Panicucci 2020 (cited previously), Tabernero et al., 2015 (cited previously), Iavarone 2015 (cited previously), Barker et al., 2018 (cited previously) and Bahleda et al., 2019 (cited previously).
Regarding instant claim 1, 22, 25, 43, and 49, App139 claim 1, 25 and 26 recite a method of treating papillary high-risk non-muscle invasive bladder cancer (HR-NMIBC), high-risk non-muscle invasive bladder cancer (HR-NMIBC), and intermediate risk non-muscle invasive bladder cancer (IR-NMIBC) the method comprising administering erdafitinib or a pharmaceutically acceptable salt thereof to a patient that is diagnosed with HR-NMIBC and that harbors at least one FGFR2 genetic alteration and/or FGFR3 genetic alteration. App139 claim 12 and 30 recite the FGFR2 genetic alteration and/or FGFR3 genetic alteration is an FGFR3 gene mutation, FGFR2 gene fusion, or FGFR3 gene fusion.
Regarding instant claim 29, App139 claim 2 and 60 recites the patient received Bacillus Calmette- Guerin (BCG) therapy prior to said administration of said erdafitinib or a pharmaceutically acceptable salt thereof.
Regarding instant claim 26, App139 claim 13 and 31 recite the FGFR3 gene mutation is R248C, S249C, G370C, Y373C, or any combination thereof. App139 claim 14 and 32 recite the FGFR2 or FGFR3 gene fusion is FGFR3- TACC3, in particular FGFR3-TACC3 V1 or FGFR3-TACC3 V3, FGFR3-BAIA P2L1, FGFR2- BICC1, FGFR2-CASP7, or any combination thereof. App139 claims 51 and 58 recite the gene fusion is FGFR3-TACC3 V1 or FGFR3- TACC3 V3.
Regarding instant claims 30 and 31, App139 claims 15, 16, 52, 54, 55, and 56 recite evaluating a biological sample from the patient for the presence of at least one of a FGFR2 genetic alteration and/or FGFR3 genetic alteration prior to said administration of the erdafitinib or a pharmaceutically acceptable salt thereof and that the biological sample is blood, lymph fluid, bone marrow, a solid tumor sample, or any combination thereof.
Regarding instant claim 34, App139 claims 17, 18, 19, 20, and 33 recite erdafitinib is administered daily, orally, and on a continuous daily dosing schedule to the patient.
Regarding instant claim 38, App139 claims 21 and 59 recite the erdafitinib is administered at a dose of about 6 mg once daily.
Regarding instant claims 41 and 42, App139 claims 23 and 24 recite erdafitinib is administered in a solid dosage form and wherein the solid dosage form is a tablet.
App139 does not recite optimizing dosages based on the patient’s age as recited in instant claims 35, 37, 38, 39, and 40. As described previously, Tabernero et al., 2015 teaches daily dose ranges from 0.5-12mg to determine the recommended phase II dose (RP2D) of erdafitinib and discloses that erdafitinib demonstrated a challenging but manageable safety profile (page 2, column 1, study design). Further, Barker et al., 2018 teaches allometric scaling method to determine pediatric doses based on PK profiles of adult doses (page 698, column 1). As Tabernero et al., 2015 teaches adult dosages and ranges with a safe tolerability profile of erdafitinib (page 5, column 1), it would have been obvious to the person of ordinary skill in the art to use allometric scaling taught by Barker et al., 2018 to determine pediatric doses based on safe and tolerable adult doses taught by Tabernero and expect reasonable success at limiting toxicities to the drug for patients under 12 years of age. Further, the dosage in a composition is clearly a result effective parameter that a person having ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been obvious for an artisan of ordinary skill to determine the optimal amount of each ingredient, i.e., the dosage and dosing regimen, needed to achieve the desired results. See MPEP §§ 2144.05; In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382; and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
App139 does not recite the cancers recited in instant claims 5, 22, and 24 and App139 does not recite the FGFR gene alteration as recited in instant claims 1, 5, 43, and 44. As described above, Panicucci 2020 teaches a method of treating cancer, said method comprising administering a therapeutically effective amount of erdafitinib to a patient who has been diagnosed with cancer and who harbors at least one fibroblast growth factor receptor (FGFR) fusion selected from claim 1 which is FGFR2-CCDC147 and the cancer is cholangiocarcinoma (page 17, paragraph 0080; page 18, paragraph 0086). Further, Bahleda et al., 2019 teaches that the erdafitinib is tolerable and preliminary clinical activity in advanced solid tumors with genomic changes in the FGFR pathway with encouraging responses in urothelial carcinoma and cholangiocarcinoma (page 4888, abstract, conclusions). It would have been obvious to the person of ordinary skill in the art to use erdafitinib to treat other cancers that harbor FGFR gene alterations and expect clinical activity against cancer.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 5, 22, 24-26, 29-31, 34-43, and 49 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 7, 8, 9, 11, 13, 25, 27, 28, 29, 31, and 33 of copending Application No. 18/044,232, herein referred to as App232 in view of Panicucci 2020 (cited previously), Tabernero et al., 2015 (cited previously), Iavarone 2015 (cited previously), Barker et al., 2018 (cited previously), FDA drug label for BALVERSA, 2019 (cited previously), and Bahleda et al., 2019 (cited previously).
Regarding instant claims 1, 5, 22, 24, 25, and 43, App232 claim 1 recites a method of treating cancer, the method comprising administering to a patient in need of cancer treatment: a fibroblast growth factor receptor (FGFR) inhibitor; an epidermal growth factor receptor (EGFR) inhibitor, wherein the cancer harbors at least one FGFR2 genetic alteration or at least one FGFR3 genetic alteration, and at least one EGFR genetic alteration.
Regarding instant claim 29, App232 claim 6, 7, and 8 recite the patient received at least one systemic therapy for the treatment of urothelial carcinoma prior to administration of the FGFR inhibitor and the EGFR inhibitor.
Regarding instant claims 25, App232 claim 9, 11, 13 recites the FGFR2 genetic alteration is a gene fusion and FGFR3 genetic alteration is a gene fusion and a gene mutation.
Regarding instant claim 30, 31, and 43, App232 claim 25 recites evaluating a biological sample from the patient for the presence of the at least one FGFR2 genetic alteration or the at least one FGFR3 genetic alteration) and at least one EGFR genetic alteration prior to administration of the FGFR inhibitor and the EGFR inhibitor.
However, App232 claim 25 does not teach the biological sample is blood, lymph fluid, bone marrow, a solid tumor sample, or any combination thereof recited in instant claim 31. As described previously, Iavarone 2015 teaches a method of treating cancer comprising obtaining a sample from the subject in need thereof to determine the level of expression of an FGFR fusion molecule in the subject prior to administering erdafitinib (page 69, paragraph 0257, column 1). Iavarone 2015 further describes that the biological sample is a tumor sample (page 4, paragraph 0045). Iavarone 2015 discloses that “the strong antitumor effects obtained with JNJ-42756493 in glioma cells harboring FGFR3-TACC3 fusions have built a compelling rationale for the treatment of glioma patients positive for FGFR-TACC rearrangements” (page 116, paragraph 0496). Therefore, it would have been obvious to the person of ordinary skill in the art to use the method of detecting FGFR fusion or genetic alteration in a sample of a cancer patient before administering erdafitinib to the patient as taught by Iavarone 2015 and expect reasonable success at inducing strong antitumor effects.
Regarding instant claim 1, 22, 41, 42, 43, and 49, App232 claim 27 recites the FGFR inhibitor is erdafitinib.
Regarding instant claim 34 and 36, App232 claims 28, 29, and 31 recite erdafitinib is administered daily and orally and wherein erdafitinib is administered orally at a dose of about 8 mg once daily.
Regarding instant claim 41, App232 claim 33 recites the erdafitinib is administered in a solid dosage form.
App232 claims do not recite the solid dosage form is a tablet in instant claim 42. Panicucci 2020 teaches that an FGFR inhibitor is a tablet which is solid dosage form (page 11, paragraph 0050) but does not teach the dosage form of the erdafitinib. The FDA drug label BALVERSA or also known as erdafitinib is in tablet form (page 1, column 1). Further, the FDA drug label BALVERSA discloses the tablets are taken daily orally and with and without food (page 1, Dosage and administration). Therefore, it would have been obvious to the person of ordinary skill in the art to include the tablet dosage form BALVERSA to allow daily oral dosage.
App232 does not recite optimizing dosages based on the patient’s age as recited in instant claims 35, 37, 38, 39, and 40. As described previously, Tabernero et al., 2015 teaches daily dose ranges from 0.5-12mg to determine the recommended phase II dose (RP2D) of erdafitinib and discloses that erdafitinib demonstrated a challenging but manageable safety profile (page 2, column 1, study design). Further, Barker et al., 2018 teaches allometric scaling method to determine pediatric doses based on PK profiles of adult doses (page 698, column 1). As Tabernero et al., 2015 teaches adult dosages and ranges with a safe tolerability profile of erdafitinib (page 5, column 1), it would have been obvious to the person of ordinary skill in the art to use allometric scaling taught by Barker et al., 2018 to determine pediatric doses based on safe and tolerable adult doses taught by Tabernero and expect reasonable success at limiting toxicities to the drug for patients under 12 years of age. Further, the dosage in a composition is clearly a result effective parameter that a person having ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been obvious for an artisan of ordinary skill to determine the optimal amount of each ingredient, i.e., the dosage and dosing regimen, needed to achieve the desired results. See MPEP §§ 2144.05; In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382; and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
App232 does not recite the cancers recited in instant claims 5, 22, and 24 and App232 does not recite the FGFR gene alteration as recited in instant claims 1, 5, 43, and 44. As described above, Panicucci 2020 teaches a method of treating cancer, said method comprising administering a therapeutically effective amount of erdafitinib to a patient who has been diagnosed with cancer and who harbors at least one fibroblast growth factor receptor (FGFR) fusion selected from claim 1 which is FGFR2-CCDC147 and the cancer is cholangiocarcinoma (page 17, paragraph 0080; page 18, paragraph 0086, and page 19, paragraph 0091). Further, Bahleda et al., 2019 teaches that the erdafitinib is tolerable and preliminary clinical activity in advanced solid tumors with genomic changes in the FGFR pathway with encouraging responses in urothelial carcinoma and cholangiocarcinoma (page 4888, abstract, conclusions). It would have been obvious to the person of ordinary skill in the art to use erdafitinib to treat other cancers that harbor FGFR gene alterations and expect clinical activity against the cancer.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 5, 22, 24-26, 29-31, 34-43, and 49 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 5, 12, 13, 14, 24, and 25 of copending Application No. 18/675,538 herein referred to as App538 in view of Panicucci 2020 (cited previously), FDA drug label for BALVERSA, 2019 (cited previously), Tabernero et al., 2015 (cited previously), Iavarone 2015 (cited previously), Barker et al., 2018 (cited previously) and Bahleda et al., 2019 (cited previously).
Regarding instant claims 1, 5, 22, 24, 25, 26, 36, 38, 43, App538 claim 1 and 24 recite a method of treating bladder cancer in a patient, the method comprising: determining that a fibroblast growth factor receptor (FGFR) single nucleotide polymorphism FGFR3 R248C is present in a biological sample from the patient, and administering a FGFR inhibitor to the patient, wherein the FGFR inhibitor comprises a compound having Structural Formula I:SN-(I), or a pharmaceutically acceptable salt thereof, wherein the method comprises administering the FGFR inhibitor to the patient according to a dosing regimen comprising a once daily dose of from about 6 mg to about 9 mg, thereby treating said bladder cancer.
Regarding instant claims 1, 22, 43, and 49, App538 claim 1, 2, 24, and 25 recite the FGFR inhibitor is a compound having the structural formula I:
PNG
media_image1.png
164
250
media_image1.png
Greyscale
. As evidentiary reference, The formula I structure is the structure of erdafitinib taught in FDA drug label for BALVERSA (page 12, Chapter 11, chemical structure of erdafitinib is shown:
PNG
media_image2.png
330
696
media_image2.png
Greyscale
).
Regarding instant claim 25, 26, and 30, App538 claim 4 and 5 recite determining that one or more additional FGFR mutants from a FGFR mutant gene panel are present in the biological sample, wherein the one or more additional FGFR mutants comprise:
a) a FGFR fusion gene comprising FGFR3:TACC3 v1, FGFR3:TACC3 v3, FGFR3:TACC3 Intron, FGFR3:BAIA P2L1, FGFR2:BICC1, FGFR2:AFF3, FGFR2:CASP7, FGFR2:CCDC6, or FGFR2:OFD1, or any combination thereof;
b) a FGFR single nucleotide polymorphism comprising FGFR3 Y373C, FGFR3 S249C or FGFR3 G370C, or any combination thereof; or
c) any combination of a) and b). App538 claim 5 recites one or more additional FGFR mutants comprise one or more of: FGFR3 Y373C, FGFR3 S249C, FGFR3 G370C, FGFR3:TACC3 vl,FGFR3:TACC3 v3, FGFR3:BAIA P2L1, FGFR2:CASP7 and FGFR2:BICC1. App538 claim 6 recites the one or more additional FGFR mutants comprise one or more of: FGFR3 Y373C, FGFR3 S249C, FGFR3 G370C, FGFR3:TACC3 v1 and FGFR3:TACC3 v3.
App538 claims do not recite the biological sample is blood, lymph fluid, bone marrow, a solid tumor sample, or any combination thereof as recited in instant claim 31. As described above, Iavarone 2015 teaches a method of treating cancer comprising obtaining a sample from the subject in need thereof to determine the level of expression of an FGFR fusion molecule in the subject prior to administering erdafitinib (page 69, paragraph 0257, column 1). Iavarone 2015 further describes that the biological sample is a tumor sample (page 4, paragraph 0045). Iavarone 2015 discloses that “the strong antitumor effects obtained with JNJ-42756493 in glioma cells harboring FGFR3-TACC3 fusions have built a compelling rationale for the treatment of glioma patients positive for FGFR-TACC rearrangements” (page 116, paragraph 0496). Therefore, it would have been obvious to the person of ordinary skill in the art to use the method of detecting FGFR fusion or genetic alteration in a sample of a cancer patient before administering erdafitinib to the patient as taught by Iavarone 2015 and expect reasonable success at inducing strong antitumor effects.
Regarding instant claims 36, 38, and 40, App538 claims 12, 13, and 14 recite administering the FGFR inhibitor to the according to a dosing regimen comprising a once daily dose of about 9 mg, once daily dose of from about 0.5 mg to about 9 mg, and once daily dose of from about 4 mg to about 9 mg.
App538 claims do not recite the solid dosage form is a tablet in instant claim 41 and 42. As described previously, Panicucci 2020 teaches that an FGFR inhibitor is a tablet which is solid dosage form (page 11, paragraph 0050) but does not teach the dosage form of the erdafitinib. The FDA drug label BALVERSA or also known as erdafitinib is in tablet form (page 1, column 1). Further, the FDA drug label BALVERSA discloses the tablets are taken daily orally and with and without food (page 1, Dosage and administration). Therefore, it would have been obvious to the person of ordinary skill in the art to include the tablet dosage form BALVERSA to allow daily oral dosage.
App538 does not recite optimizing dosages based on the patient’s age as recited in instant claims 35, 37, 38, 39, and 40. As described previously, Tabernero et al., 2015 teaches daily dose ranges from 0.5-12mg to determine the recommended phase II dose (RP2D) of erdafitinib and discloses that erdafitinib demonstrated a challenging but manageable safety profile (page 2, column 1, study design). Further, Barker et al., 2018 teaches allometric scaling method to determine pediatric doses based on PK profiles of adult doses (page 698, column 1). As Tabernero et al., 2015 teaches adult dosages and ranges with a safe tolerability profile of erdafitinib (page 5, column 1), it would have been obvious to the person of ordinary skill in the art to use allometric scaling taught by Barker et al., 2018 to determine pediatric doses based on safe and tolerable adult doses taught by Tabernero and expect reasonable success at limiting toxicities to the drug for patients under 12 years of age. Further, the dosage in a composition is clearly a result effective parameter that a person having ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been obvious for an artisan of ordinary skill to determine the optimal amount of each ingredient, i.e., the dosage and dosing regimen, needed to achieve the desired results. See MPEP §§ 2144.05; In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382; and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
App538 does not recite the subject received at least one line of systemic therapy prior to said administration of erdafitinib as recited in instant claim 29. As described previously, Panicucci 2020 teaches that the subject received at least one line of systemic therapy prior to administration of erdafitinib (page 18, paragraph 0083). Panicucci 2020 teaches that cholangiocarcinoma patients relapse after first line of therapy and have few therapeutic options (page 3, line 29-31). It would have been obvious to the person of ordinary skill in the art to use erdafitinib in patients with cholangiocarcinoma that relapsed after first line therapy and have few options for second line standard of care.
App538 does not recite the cancers recited in instant claims 5, 22, and 24 and App538 does not recite the FGFR gene alteration as recited in instant claims 1, 5, 43, and 44. As described above, Panicucci 2020 teaches a method of treating cancer, said method comprising administering a therapeutically effective amount of erdafitinib to a patient who has been diagnosed with cancer and who harbors at least one fibroblast growth factor receptor (FGFR) fusion selected from claim 1 which is FGFR2-CCDC147 and the cancer is cholangiocarcinoma (page 17, paragraph 0080; page 18, paragraph 0086, and page 19, paragraph 0091). Further, Bahleda et al., 2019 teaches that the erdafitinib is tolerable and preliminary clinical activity in advanced solid tumors with genomic changes in the FGFR pathway with encouraging responses in urothelial carcinoma and cholangiocarcinoma (page 4888, abstract, conclusions). It would have been obvious to the person of ordinary skill in the art to use erdafitinib to treat other cancers that harbor FGFR gene alterations and expect clinical activity against cancers.
This is a provisional nonstatutory double patenting rejection.
Allowable Subject Matter
Claim 44 is objected to as to being dependent upon a rejected base claim 43, but the claim objection could overcome the rejected base claim if rewritten in independent form including all of the limitations of the base claim and any intervening claims. The following is a statement of reasons for the indication of allowable subject matter: The FGFR fusions “FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1” as recited in claim 44 was found free of the prior art. The closest prior art is US 2015/0315657 A1, published on 11/5/2015, herein referred to as Rhodes 2015. Rhodes 2015 teaches a method of detecting gene fusion proteins in a biological sample and detecting gene fusions found in cancer and administer drugs to target the gene fusions, one of which is FGFR and PDE3A in lung adenocarcinoma as one of the gene fusions and erdafitinib as the drug (page 4, paragraph 0034, “In one embodiment, a method is provided, wherein the method comprises administering to a patient having at least one gene fusion selected from the gene fusions listed in Tables 1-3, 19, and 22 at least one drug selected from the drugs listed in Tables 8, 16-17, 21, and 24” and see Table 8, page 62 and Table 19, page 109).
PNG
media_image3.png
432
532
media_image3.png
Greyscale
Figure 1 Druggable genes from Rhodes 2015 (page 62)
PNG
media_image4.png
358
342
media_image4.png
Greyscale
Figure 2 Gene Fusions in Rhodes 2015 (page 109)
However, Rhodes 2015 does not teach the FGFR fusion FGFR2-PDE3A. Applicant’s disclosure teaches that the FGFR2-PDE3A fusion protein is found in a patient with cholangiocarcinoma (specification, page 156, Table 9) which Rhodes 2015 does not teach.
Prior to the effective filing date of the invention, one of ordinary skill in the art would not be able to predict the detection the FGFR fusion proteins “FGFR2-CCDC102A, FGFR2-ENOX1, FGFR2-GPHN, FGFR2-PDE3A, FGFR3-ENOX1, FGFR3-TMEM247, IGSF3-FGFR1, and RHPN2-FGFR1” in a biological sample of a patient who has been diagnosed with cancer and administered a therapeutically effective amount of erdafitinib to the patient if at least one of the FGFR fusion protein is present in the sample. Therefore, Claim 44 contains allowable subject matter.
Conclusion
Claims 1, 5, 22, 24, 25, 26, 29, 30, 31, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, and 49 are rejected. Claim 44 limitation is free of the prior art and contains allowable subject matter.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Lam Thuy Vi Tran Ho whose telephone number is (571)272-9135. The examiner can normally be reached Monday-Friday 7:30-3.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached at (571) 272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LAM THUY VI TRAN HO/Examiner, Art Unit 1647 /L.T./Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
Prosecution Insights